Is ATF2 p.Val211Leu (c.631G>T) pathogenic?

ATF2 p.Val211Leu (c.631G>T) is classified Uncertain significance in ATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1796); Absent from gnomAD v4.1.

How common is ATF2 p.Val211Leu (c.631G>T) in the general population?

ATF2 p.Val211Leu (c.631G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF2 p.Val211Leu (c.631G>T)?

AlphaMissense predicts likely benign (score 0.1796) — an in-silico prediction, not a clinical call.

ATF2 p.Val211Leu

c.631G>T · VCV4161881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1796 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1796	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -7.28	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 7.7	GERP 1.1, phastCons 1
Overall
CADD	22.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATF2
Protein: p.Val211Leu
Coding: c.631G>T
MANE Select: NM_000514 · reported on NM_001880
Type: single nucleotide variant
Location: chr2:175114104 (GRCh38)
Structure: AlphaFold pLDDT 75.29 · 4 PDB
Residue 211: a UniProt-annotated variant site (in hscr3)

Full ATF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GDNF p.Ile211Met 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/atf2-p-val211leu (accessed [today's date]).

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