Is ATF1 p.Val97Ile (c.289G>A) pathogenic?

ATF1 p.Val97Ile (c.289G>A) is classified Uncertain significance in ATF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.0843); Ultra-rare (popmax 0.033%, mid).

How common is ATF1 p.Val97Ile (c.289G>A) in the general population?

ATF1 p.Val97Ile (c.289G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ATF1 p.Val97Ile (c.289G>A)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

ATF1 p.Val97Ile

c.289G>A · rs369352834 · VCV2522164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.33	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 6.3	GERP 2.5, phastCons 1
Overall
CADD	22.2	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 0.033% Middle Eastern · 2/6,068 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00155% 25/1,613,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,034
Admixed American	0.01%	9,992
Remaining individualsnot grpmax-eligible	0.0032%	31,233
African / African-American	0.00267%	37,452
European (non-Finnish)	0.0011%	90,753

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: ATF1
Protein: p.Val97Ile
Coding: c.289G>A
MANE Select: NM_000514 · reported on NM_005171
dbSNP: rs369352834
Type: single nucleotide variant
Location: chr12:50809550 (GRCh38)
Structure: AlphaFold pLDDT 75.29 · 4 PDB
Residue 97: the 'disordered' region

Full ATF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF1 p.Val97Phe Uncertain significance ★ ⚠ same residue
GDNF c.*2213G>A Uncertain significance ★★ same type
GDNF c.*2828T>A Uncertain significance ★★ same type
GDNF p.Arg116Gln Uncertain significance ★★ ⚠ same type
ATF1 p.Tyr109= Benign ★★ same type
ATF2 p.Asn348= Benign ★★ same type
ATF2 p.Asp440= Benign ★★ same type
GDNF c.152-73C>T Benign ★★ 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/atf1-p-val97ile (accessed [today's date]).

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