Is SEC31A p.Pro810Ser (c.2428C>T) pathogenic?

SEC31A p.Pro810Ser (c.2428C>T) is classified Uncertain significance in SEC31A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely benign (0.0714); Ultra-rare (popmax 0.0174%, afr).

How common is SEC31A p.Pro810Ser (c.2428C>T) in the general population?

SEC31A p.Pro810Ser (c.2428C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about SEC31A p.Pro810Ser (c.2428C>T)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

SEC31A p.Pro810Ser

c.2428C>T · VCV3317151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.04	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 0.14	GERP -1.4, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 63 kb · p 0.00023 · regional, not allelic
Overall
CADD	12.63	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 0.0174% African / African-American · 13/74,880 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000929% 15/1,613,942 alleles · ultra-rare exomes 7/1,461,854 · genomes 8/152,088 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,760
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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.Pro810Ser
Coding: c.2428C>T
MANE Select: NM_001077207
Type: single nucleotide variant
Location: chr4:82848878 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 68.95 · 2 PDB
Residue 810: the 'disordered' region; the 'interaction with pdcd6' 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-pro810ser (accessed [today's date]).

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