Is ATF6 p.Ser97Pro (c.289T>C) pathogenic?

ATF6 p.Ser97Pro (c.289T>C) is classified Uncertain significance in ATF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-13). AlphaMissense: likely benign (0.0931); Absent from gnomAD v4.1.

How common is ATF6 p.Ser97Pro (c.289T>C) in the general population?

ATF6 p.Ser97Pro (c.289T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF6 p.Ser97Pro (c.289T>C)?

AlphaMissense predicts likely benign (score 0.0931) — an in-silico prediction, not a clinical call.

ATF6 p.Ser97Pro

c.289T>C · rs1684692967 · VCV966916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0931	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.85	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 1.8	GERP 2.3, phastCons 0.87
Regional constraint	o/e 0.93	unconstrained · MANE · 192 kb · p 0.056 · regional, not allelic
Overall
CADD	16.79	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: ATF6
Protein: p.Ser97Pro
Coding: c.289T>C
MANE Select: NM_007348
dbSNP: rs1684692967
Type: single nucleotide variant
Location: chr1:161784031 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 97: the 'transcription activation' region; the 'disordered' region

Full ATF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF6 c.1533+1G>C Pathogenic ★★ same type
ATF6 c.160-1G>A Likely pathogenic ★★ same type
ATF6 c.484+1G>A Likely pathogenic ★★ same type
ATF6 c.484+1G>T Likely pathogenic ★★ same type
ATF6 c.82+5G>T Pathogenic ★★ same type
ATF6 p.Arg324Cys Pathogenic ★★ same type
ATF6 p.Arg376Ter Pathogenic ★★ same type
ATF6 p.Gln237Ter Pathogenic ★★ 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/atf6-p-ser97pro (accessed [today's date]).

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