Is SEC31A p.Ser233= (c.699C>T) pathogenic?

SEC31A p.Ser233= (c.699C>T) is classified Likely benign in SEC31A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0111%, nfe).

How common is SEC31A p.Ser233= (c.699C>T) in the general population?

SEC31A p.Ser233= (c.699C>T) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

SEC31A p.Ser233=

c.699C>T · rs755744216 · VCV2654853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP -1.1, phastCons 0.83
Overall
CADD	13.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% European (non-Finnish) · 131/1,179,940 alleles

Filtering AF 0.00953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00896%

Overall 0.00923% 149/1,613,888 alleles · ultra-rare exomes 145/1,461,784 · genomes 4/152,104 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)grpmax	0.0111%	9,007
South Asian	0.00329%	30,361
East Asian	0.00223%	44,882

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser233=
Coding: c.699C>T
MANE Select: NM_001077207
dbSNP: rs755744216
Type: single nucleotide variant
Location: chr4:82872027 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 68.95 · 2 PDB
Residue 233: a β-strand; 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-ser233 (accessed [today's date]).

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