Is ATF3 p.Ser24Phe (c.71C>T) pathogenic?

ATF3 p.Ser24Phe (c.71C>T) is classified Uncertain significance in ATF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: ambiguous (0.372); Ultra-rare (popmax 0.016%, afr).

How common is ATF3 p.Ser24Phe (c.71C>T) in the general population?

ATF3 p.Ser24Phe (c.71C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about ATF3 p.Ser24Phe (c.71C>T)?

AlphaMissense predicts ambiguous (score 0.372) — an in-silico prediction, not a clinical call.

ATF3 p.Ser24Phe

c.71C>T · VCV4643736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.372 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Computational evidence

Protein change
AlphaMissense	0.372	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -10.83	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 4,530 bp · p 0.0084 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,896 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000805% 13/1,614,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,241
European (non-Finnish)	8.47e-05%	1,180,043

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: ATF3
Protein: p.Ser24Phe
Coding: c.71C>T
MANE Select: NM_001674
Type: single nucleotide variant
Location: chr1:212615092 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 77.45

Full ATF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF3 p.Ser24Cys Uncertain significance ★ ⚠ same residue
ATF3 p.Ser24= Likely benign same residue
ATF3 p.Ser12Pro Uncertain significance ★★ ⚠ same type
ATF3 p.Ala82Val Uncertain significance ★ ⚠ same type
ATF3 p.Asn168Ile Uncertain significance ★ ⚠ same type
ATF3 p.Asp69Asn Uncertain significance ★ ⚠ same type
ATF3 p.Gln115Glu Uncertain significance ★ ⚠ same type
ATF3 p.Glu32Lys 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/atf3-p-ser24phe (accessed [today's date]).

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