Is ATF1 p.Pro163Ser (c.487C>T) pathogenic?

ATF1 p.Pro163Ser (c.487C>T) is classified Uncertain significance in ATF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: likely pathogenic (0.8123); Absent from gnomAD v4.1.

How common is ATF1 p.Pro163Ser (c.487C>T) in the general population?

ATF1 p.Pro163Ser (c.487C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF1 p.Pro163Ser (c.487C>T)?

AlphaMissense predicts likely pathogenic (score 0.8123) — an in-silico prediction, not a clinical call.

ATF1 p.Pro163Ser

c.487C>T · VCV3795863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8123 · 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	0.8123	likely pathogenic
REVEL	0.346	indeterminate
SaProt	LLR -10.18	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 5.9	GERP 0.75, phastCons 1
Overall
CADD	24.7	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: ATF1
Protein: p.Pro163Ser
Coding: c.487C>T
MANE Select: NM_000514 · reported on NM_005171
Type: single nucleotide variant
Location: chr12:50814168 (GRCh38)
Structure: AlphaFold pLDDT 75.29 · 4 PDB
Residue 163: a disulfide bond; an α-helix

Full ATF1 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/atf1-p-pro163ser (accessed [today's date]).

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