Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000277.1(PAH):c.716G>T (p.Gly239Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229711

102800 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: fb82abb9-c0f3-4901-acad-0e2a6de4b34d

Approved on: 2020-10-23

Published on: 2020-10-23

HGVS expressions

NM_000277.1:c.716G>T

NM_000277.1(PAH):c.716G>T (p.Gly239Val)

NC_000012.12:g.102852941C>A

CM000674.2:g.102852941C>A

NC_000012.11:g.103246719C>A

CM000674.1:g.103246719C>A

NC_000012.10:g.101770849C>A

NG_008690.1:g.69662G>T

NG_008690.2:g.110470G>T

NM_000277.2:c.716G>T

NM_001354304.1:c.716G>T

NM_000277.3:c.716G>T

NM_001354304.2:c.716G>T

ENST00000307000.7:c.701G>T

ENST00000549247.6:n.475G>T

ENST00000553106.5:c.716G>T

Likely Pathogenic

PP4 PP3 PM2 PM3

PM5

Evidence Links 3

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.716G>T (p.Gly239Val) variant in PAH has been reported in 2 individuals with classic PKU (PMID 10394930, 31623983) detected with pathogenic variants p.R408W and IVS10–11g>a (PMID: 32106880). This variant has extremely low frequency in gnomAD (MAF=0.00006). Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PP3.

PP4

PMID 10394930: In Table 1, listed on allele of p.Gly239Val in a cohort of Germany PKU/HPA patients. PMID: 31623983 Detected in a classic PKU patient at Boston Children's. BH4 deficiency not reportedly ruled out PMID: 32106880

In Table 1, listed on allele of p.Gly239Val in a cohort of Germany PKU/HPA patients. PubMed:10394930

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.978

PM2

extremely low frequency in GnomAD (MAF=0.00006)

PM3

detected with p.R408W (P 14 submitters) PMID: 31623983 IVS10–11g>a (P 7 submitters) PMID: 32106880 parental analysis not reported

PubMed:31623983

PubMed:32106880

PM5

p.Gly239Ala/Ser/Asp no interpretation in ClinVar

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.