Is ATF2 p.Ala481Val (c.1442C>T) pathogenic?

ATF2 p.Ala481Val (c.1442C>T) is classified Uncertain significance in ATF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely benign (0.2531); Very rare (popmax 0.0011%, sas).

How common is ATF2 p.Ala481Val (c.1442C>T) in the general population?

ATF2 p.Ala481Val (c.1442C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ATF2 p.Ala481Val (c.1442C>T)?

AlphaMissense predicts likely benign (score 0.2531) — an in-silico prediction, not a clinical call.

ATF2 p.Ala481Val

c.1442C>T · VCV3320422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2531	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Overall
CADD	24.2	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 0.0011% South Asian · 1/91,074 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,178 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	0.00017%	589,835

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.Ala481Val
Coding: c.1442C>T
MANE Select: NM_000514 · reported on NM_001880
Type: single nucleotide variant
Location: chr2:175074685 (GRCh38)
Structure: AlphaFold pLDDT 75.29 · 4 PDB

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

Similar variants

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
GDNF c.-51A>G 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-ala481val (accessed [today's date]).

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