Is ATMIN p.Gly331Asp (c.992G>A) pathogenic?

ATMIN p.Gly331Asp (c.992G>A) is classified Uncertain significance in ATMIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: ambiguous (0.3613); Very rare (popmax 8.47e-05%, nfe).

How common is ATMIN p.Gly331Asp (c.992G>A) in the general population?

ATMIN p.Gly331Asp (c.992G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ATMIN p.Gly331Asp (c.992G>A)?

AlphaMissense predicts ambiguous (score 0.3613) — an in-silico prediction, not a clinical call.

ATMIN p.Gly331Asp

c.992G>A · VCV4170840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3613	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,096 bp · p 0.32 · regional, not allelic
Overall
CADD	22.0	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 0.00041% 6/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,400
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,038

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ATMIN
Protein: p.Gly331Asp
Coding: c.992G>A
MANE Select: NM_015251
Type: single nucleotide variant
Location: chr16:81043490 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.67
Residue 331: the 'required for formation of rad51 foci' region

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

Similar variants

ATMIN p.Ala10Glu Uncertain significance ★ ⚠ same type
ATMIN p.Ala16Val Uncertain significance ★ ⚠ same type
ATMIN p.Ala19Gly Uncertain significance ★ ⚠ same type
ATMIN p.Ala302Val Uncertain significance ★ ⚠ same type
ATMIN p.Ala340Thr Uncertain significance ★ ⚠ same type
ATMIN p.Ala359Thr Uncertain significance ★ ⚠ same type
ATMIN p.Ala3Gly Uncertain significance ★ ⚠ same type
ATMIN p.Ala431Thr 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/atmin-p-gly331asp (accessed [today's date]).

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