Is ATMIN p.Phe694Leu (c.2080T>C) pathogenic?

ATMIN p.Phe694Leu (c.2080T>C) is classified Uncertain significance in ATMIN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-21). AlphaMissense: likely pathogenic (0.7522); Very rare (popmax 0.00667%, amr).

How common is ATMIN p.Phe694Leu (c.2080T>C) in the general population?

ATMIN p.Phe694Leu (c.2080T>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ATMIN p.Phe694Leu (c.2080T>C)?

AlphaMissense predicts likely pathogenic (score 0.7522) — an in-silico prediction, not a clinical call.

ATMIN p.Phe694Leu

c.2080T>C · rs780741451 · VCV2227586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7522 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7522	likely pathogenic
REVEL	0.163	moderately benign-leaning
SaProt	LLR -5.15	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,096 bp · p 0.32 · regional, not allelic
Overall
CADD	19.66	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 0.00667% Admixed American · 4/59,980 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,613,968 alleles · very rare

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.Phe694Leu
Coding: c.2080T>C
MANE Select: NM_015251
dbSNP: rs780741451
Type: single nucleotide variant
Location: chr16:81044578 (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-phe694leu (accessed [today's date]).

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