Is ATMIN p.Leu656Pro (c.1967T>C) pathogenic?

ATMIN p.Leu656Pro (c.1967T>C) is classified Uncertain significance in ATMIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: likely benign (0.3249); Very rare (popmax 0.00297%, nfe).

How common is ATMIN p.Leu656Pro (c.1967T>C) in the general population?

ATMIN p.Leu656Pro (c.1967T>C) is very rare (popmax 0.00297%, nfe) (gnomAD).

What do computational predictors say about ATMIN p.Leu656Pro (c.1967T>C)?

AlphaMissense predicts likely benign (score 0.3249) — an in-silico prediction, not a clinical call.

ATMIN p.Leu656Pro

c.1967T>C · VCV4170829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3249	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,096 bp · p 0.32 · regional, not allelic
Overall
CADD	23.8	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 0.00297% European (non-Finnish) · 35/1,179,966 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00223% 36/1,613,734 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,713
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Leu656Pro
Coding: c.1967T>C
MANE Select: NM_015251
Type: single nucleotide variant
Location: chr16:81044465 (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.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-leu656pro (accessed [today's date]).

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