Is PGK1 p.Val247Ala (c.740T>C) pathogenic?

PGK1 p.Val247Ala (c.740T>C) is classified Uncertain significance in PGK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: ambiguous (0.5458); No allele count reported in gnomAD v4.1 (AN 1,147,866); Associated with PGK1-related disorder.

What condition is associated with PGK1 p.Val247Ala (c.740T>C)?

PGK1 p.Val247Ala (c.740T>C) is associated with PGK1-related disorder (ClinVar).

How common is PGK1 p.Val247Ala (c.740T>C) in the general population?

PGK1 p.Val247Ala (c.740T>C) is no allele count reported in gnomAD v4.1 (AN 1,147,866) (gnomAD).

What do computational predictors say about PGK1 p.Val247Ala (c.740T>C)?

AlphaMissense predicts ambiguous (score 0.5458) — an in-silico prediction, not a clinical call.

PGK1 p.Val247Ala

c.740T>C · rs2078363408 · VCV2631729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5458 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,147,866)

Conditions

PGK1-related disorder

Computational evidence

Protein change
AlphaMissense	0.5458	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -11.13	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 5,092 bp · p 2.4e-05 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,147,866). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGK1
Protein: p.Val247Ala
Coding: c.740T>C
MANE Select: NM_000291
dbSNP: rs2078363408
Type: single nucleotide variant
Location: chrX:78122933 (GRCh38)
Structure: AlphaFold pLDDT 96.48 · 30 PDB
Residue 247: an α-helix

Full PGK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PGK1-related disorder

Similar variants

PGK1 p.Asn26Ser Uncertain significance ★★ ⚠ same condition
PGK1 p.Gly366Arg Uncertain significance ★★ ⚠ same condition
PGK1 p.Asn249Lys Uncertain significance ★ ⚠ same condition
PGK1 p.Gly213= Conflicting classifications of pathogenicity ★ same condition
PGK1 p.Ile334Val Uncertain significance ⚠ same condition
PGK1 p.Lys192del Conflicting classifications of pathogenicity same condition
PGK1 p.Asp164Val Pathogenic ★★ same type
PGK1 c.116+2T>C Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pgk1-p-val247ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown