Is ATF3 p.Leu146Phe (c.436C>T) pathogenic?

ATF3 p.Leu146Phe (c.436C>T) is classified Uncertain significance in ATF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely pathogenic (0.9964); Absent from gnomAD v4.1.

How common is ATF3 p.Leu146Phe (c.436C>T) in the general population?

ATF3 p.Leu146Phe (c.436C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF3 p.Leu146Phe (c.436C>T)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

ATF3 p.Leu146Phe

c.436C>T · rs2527467012 · VCV3130789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 6% in ATF3
REVEL	0.604	indeterminate
SaProt	LLR -11.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 4,530 bp · p 0.0084 · regional, not allelic
Overall
CADD	28.4	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

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: ATF3
Protein: p.Leu146Phe
Coding: c.436C>T
MANE Select: NM_001674
dbSNP: rs2527467012
Type: single nucleotide variant
Location: chr1:212619445 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 77.45
Residue 146: the bzip domain

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

Similar variants

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
ATF3 p.Glu80Lys Uncertain significance ★ ⚠ same type
ATF3 p.Ile171Thr 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-leu146phe (accessed [today's date]).

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