Is ATMIN p.Thr461Ala (c.1381A>G) pathogenic?

ATMIN p.Thr461Ala (c.1381A>G) is classified Uncertain significance in ATMIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: ambiguous (0.4751); Very rare (popmax 0.00627%, nfe).

How common is ATMIN p.Thr461Ala (c.1381A>G) in the general population?

ATMIN p.Thr461Ala (c.1381A>G) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about ATMIN p.Thr461Ala (c.1381A>G)?

AlphaMissense predicts ambiguous (score 0.4751) — an in-silico prediction, not a clinical call.

ATMIN p.Thr461Ala

c.1381A>G · VCV3326912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4751	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -7.98	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,096 bp · p 0.32 · regional, not allelic
Overall
CADD	23.2	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 0.00627% European (non-Finnish) · 74/1,180,060 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00471% 76/1,614,078 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00627%	15,947
African / African-American	0.00267%	37,451

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.Thr461Ala
Coding: c.1381A>G
MANE Select: NM_015251
Type: single nucleotide variant
Location: chr16:81043879 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.67

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

Similar variants

ATMIN p.Thr461Ile Uncertain significance ★ ⚠ same residue
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

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-thr461ala (accessed [today's date]).

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