Is SEC31A p.Ser397Ala (c.1189T>G) pathogenic?

SEC31A p.Ser397Ala (c.1189T>G) is classified Uncertain significance in SEC31A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.1599); Absent from gnomAD v4.1.

How common is SEC31A p.Ser397Ala (c.1189T>G) in the general population?

SEC31A p.Ser397Ala (c.1189T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SEC31A p.Ser397Ala (c.1189T>G)?

AlphaMissense predicts likely benign (score 0.1599) — an in-silico prediction, not a clinical call.

SEC31A p.Ser397Ala

c.1189T>G · rs1241122120 · VCV2537931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1599 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1599	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 63 kb · p 0.00023 · regional, not allelic
Overall
CADD	23.1	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: SEC31A
Protein: p.Ser397Ala
Coding: c.1189T>G
MANE Select: NM_001077207
dbSNP: rs1241122120
Type: single nucleotide variant
Location: chr4:82866816 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 68.95 · 2 PDB
Residue 397: the 'interaction with sec13' region

Full SEC31A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC31A p.Arg486His Uncertain significance ★★ same type
SEC31A p.Asp84Gly Uncertain significance ★★ ⚠ same type
SEC31A p.Cys458Trp Uncertain significance ★★ ⚠ same type
SEC31A p.Pro945Ser Uncertain significance ★★ ⚠ same type
SEC31A c.1045-26G>T Benign ★★ same type
SEC31A c.2154+36G>C Benign ★★ same type
SEC31A c.2154+8C>T Likely benign ★★ same type
SEC31A c.2503-29C>A 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/sec31a-p-ser397ala (accessed [today's date]).

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