Is PGM2 p.Ala121Val (c.362C>T) pathogenic?

PGM2 p.Ala121Val (c.362C>T) is classified Uncertain significance in PGM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.7869); Ultra-rare (popmax 0.033%, sas).

How common is PGM2 p.Ala121Val (c.362C>T) in the general population?

PGM2 p.Ala121Val (c.362C>T) is ultra-rare (popmax 0.033%, sas) (gnomAD).

What do computational predictors say about PGM2 p.Ala121Val (c.362C>T)?

AlphaMissense predicts likely pathogenic (score 0.7869) — an in-silico prediction, not a clinical call.

PGM2 p.Ala121Val

c.362C>T · VCV3888103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7869 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7869	likely pathogenic
REVEL	0.781	moderately pathogenic-leaning
SaProt	LLR -10.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 18 kb · p 0.87 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% South Asian · 30/90,962 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00187% 30/1,608,456 alleles · ultra-rare exomes 28/1,456,264 · genomes 2/152,192 · 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: PGM2
Protein: p.Ala121Val
Coding: c.362C>T
MANE Select: NM_018290
Type: single nucleotide variant
Location: chr4:37837534 (GRCh38)
Gene constraint: LOEUF 1.172 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.60

Full PGM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGM2 p.Asp322= Benign ★★ same type
PGM2 p.Ala107Thr Uncertain significance ★ ⚠ same type
PGM2 p.Ala124Thr Uncertain significance ★ ⚠ same type
PGM2 p.Ala277Val Uncertain significance ★ ⚠ same type
PGM2 p.Ala2Gly Uncertain significance ★ ⚠ same type
PGM2 p.Ala310Asp Uncertain significance ★ ⚠ same type
PGM2 p.Ala315Asp Uncertain significance ★ ⚠ same type
PGM2 p.Ala325Val 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/pgm2-p-ala121val (accessed [today's date]).

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