Is GPAM p.Val511Met (c.1531G>A) pathogenic?

GPAM p.Val511Met (c.1531G>A) is classified Uncertain significance in GPAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). AlphaMissense: likely benign (0.0952); Very rare (popmax 0.00333%, amr).

How common is GPAM p.Val511Met (c.1531G>A) in the general population?

GPAM p.Val511Met (c.1531G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about GPAM p.Val511Met (c.1531G>A)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

GPAM p.Val511Met

c.1531G>A · VCV3854837

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 28 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00093% 15/1,613,630 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
South Asian	0.0011%	91,078
European (non-Finnish)	0.00102%	98,307

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: GPAM
Protein: p.Val511Met
Coding: c.1531G>A
MANE Select: NM_001244949
Type: single nucleotide variant
Location: chr10:112160832 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 2 PDB
Residue 511: an α-helix

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

Similar variants

GPAM p.Ala420Val Benign ★★ same type
GPAM p.Asp399= Benign ★★ same type
GPAM p.Ile43Val Benign ★★ same type
GPAM c.102+1G>A Uncertain significance ★ same type
GPAM p.Ala144Thr Uncertain significance ★ ⚠ same type
GPAM p.Ala144Val Uncertain significance ★ ⚠ same type
GPAM p.Ala327Thr Uncertain significance ★ ⚠ same type
GPAM p.Ala382Thr 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/gpam-p-val511met (accessed [today's date]).

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