Is SEC31A p.Pro945Ser (c.2833C>T) pathogenic?

SEC31A p.Pro945Ser (c.2833C>T) is classified Uncertain significance in SEC31A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-28). AlphaMissense: likely benign (0.068); Ultra-rare (popmax 0.0601%, afr).

How common is SEC31A p.Pro945Ser (c.2833C>T) in the general population?

SEC31A p.Pro945Ser (c.2833C>T) is ultra-rare (popmax 0.0601%, afr) (gnomAD).

What do computational predictors say about SEC31A p.Pro945Ser (c.2833C>T)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

SEC31A p.Pro945Ser

c.2833C>T · rs150467054 · VCV2637544

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0601%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -7.83	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 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 63 kb · p 0.00023 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.0601% African / African-American · 45/74,906 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00304% 49/1,613,902 alleles · ultra-rare exomes 26/1,461,746 · genomes 23/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0601%	1,665
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	59,978

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: SEC31A
Protein: p.Pro945Ser
Coding: c.2833C>T
MANE Select: NM_001077207
dbSNP: rs150467054
Type: single nucleotide variant
Location: chr4:82842275 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 68.95 · 2 PDB
Residue 945: the 'interaction with pdcd6' region; the 'disordered' 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 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
SEC31A c.640-4T>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/sec31a-p-pro945ser (accessed [today's date]).

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