Is PGAM1 p.Ala2Val (c.5C>T) pathogenic?

PGAM1 p.Ala2Val (c.5C>T) is classified Uncertain significance in PGAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: ambiguous (0.5201); Very rare (popmax 0.000933%, nfe).

How common is PGAM1 p.Ala2Val (c.5C>T) in the general population?

PGAM1 p.Ala2Val (c.5C>T) is very rare (popmax 0.000933%, nfe) (gnomAD).

What do computational predictors say about PGAM1 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.5201) — an in-silico prediction, not a clinical call.

PGAM1 p.Ala2Val

c.5C>T · VCV4567059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5201	ambiguous · top 4% in PGAM1
REVEL	0.547	indeterminate
SaProt	LLR -9.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Overall
CADD	21.8	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

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,220 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000683% 11/1,610,434 alleles · very rare exomes 11/1,458,064 · genomes 0/152,370 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PGAM1
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_002629
Type: single nucleotide variant
Location: chr10:97426312 (GRCh38)
Structure: AlphaFold pLDDT 94.21

Full PGAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAM1 p.Asn99= Benign ★★ same type
PGAM1 p.Ser152= Benign ★★ same type
PGAM1 p.Ala105Gly Uncertain significance ★ ⚠ same type
PGAM1 p.Ala105Val Uncertain significance ★ ⚠ same type
PGAM1 p.Ala163Thr Uncertain significance ★ ⚠ same type
PGAM1 p.Ala248Thr Uncertain significance ★ ⚠ same type
PGAM1 p.Ala48Val Uncertain significance ★ ⚠ same type
PGAM1 p.Ala73Gly 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/pgam1-p-ala2val (accessed [today's date]).

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