Is ATF2 p.Pro232Arg (c.695C>G) pathogenic?

ATF2 p.Pro232Arg (c.695C>G) is classified Uncertain significance in ATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). AlphaMissense: likely pathogenic (0.9004); Very rare (popmax 0.00134%, afr).

How common is ATF2 p.Pro232Arg (c.695C>G) in the general population?

ATF2 p.Pro232Arg (c.695C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ATF2 p.Pro232Arg (c.695C>G)?

AlphaMissense predicts likely pathogenic (score 0.9004) — an in-silico prediction, not a clinical call.

ATF2 p.Pro232Arg

c.695C>G · VCV3795890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9004 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9004	likely pathogenic
REVEL	0.565	indeterminate
SaProt	LLR -12.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 0.00032 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00134% African / African-American · 1/74,746 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00093% 15/1,612,762 alleles · very rare exomes 13/1,460,842 · genomes 2/151,920 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,746
European (non-Finnish)	0.00119%	84,264

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: ATF2
Protein: p.Pro232Arg
Coding: c.695C>G
MANE Select: NM_001880
Type: single nucleotide variant
Location: chr2:175114040 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 58.58 · 8 PDB

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

Similar variants

ATF2 p.Asn348= Benign ★★ same type
ATF2 p.Asp440= Benign ★★ same type
ATF2 c.742-2A>G Uncertain significance ★ same type
ATF2 p.Ala244Thr Uncertain significance ★ ⚠ same type
ATF2 p.Ala422Thr Uncertain significance ★ ⚠ same type
ATF2 p.Ala422Val Uncertain significance ★ ⚠ same type
ATF2 p.Ala469Val Uncertain significance ★ ⚠ same type
ATF2 p.Ala481Val 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/atf2-p-pro232arg (accessed [today's date]).

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