Is PGAM2 p.Val112Met (c.334G>A) pathogenic?

PGAM2 p.Val112Met (c.334G>A) is classified Uncertain significance in PGAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely pathogenic (0.9811); Very rare (popmax 0.00534%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAM2 p.Val112Met (c.334G>A)?

PGAM2 p.Val112Met (c.334G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PGAM2 p.Val112Met (c.334G>A) in the general population?

PGAM2 p.Val112Met (c.334G>A) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about PGAM2 p.Val112Met (c.334G>A)?

AlphaMissense predicts likely pathogenic (score 0.9811) — an in-silico prediction, not a clinical call.

PGAM2 p.Val112Met

c.334G>A · VCV3305923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9811	likely pathogenic
REVEL	0.678	pathogenic-leaning
SaProt	LLR -14.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,762 bp · p 0.7 · regional, not allelic
Overall
CADD	28.3	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 0.00534% European (non-Finnish) · 63/1,180,056 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00409% 66/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,731
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,934
South Asian	0.0011%	91,092

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: PGAM2
Protein: p.Val112Met
Coding: c.334G>A
MANE Select: NM_001014436 · reported on NM_000290
Type: single nucleotide variant
Location: chr7:44065196 (GRCh38)

Full PGAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/pgam2-p-val112met (accessed [today's date]).

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