Is ATF2 p.Ala244Thr (c.730G>A) pathogenic?

ATF2 p.Ala244Thr (c.730G>A) is classified Uncertain significance in ATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0718); Absent from gnomAD v4.1.

How common is ATF2 p.Ala244Thr (c.730G>A) in the general population?

ATF2 p.Ala244Thr (c.730G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF2 p.Ala244Thr (c.730G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

ATF2 p.Ala244Thr

c.730G>A · VCV4161860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.00	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 3.3	GERP 0.94, phastCons 1
Overall
CADD	19.29	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.Ala244Thr
Coding: c.730G>A
MANE Select: NM_000514 · reported on NM_001880
Type: single nucleotide variant
Location: chr2:175114005 (GRCh38)
Structure: AlphaFold pLDDT 75.29 · 4 PDB

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

Similar variants

ATF1 p.Arg244Gly 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-ala244thr (accessed [today's date]).

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