Is SEC24C p.Pro255Ala (c.763C>G) pathogenic?

SEC24C p.Pro255Ala (c.763C>G) is classified Benign in SEC24C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-04). AlphaMissense: likely benign (0.0684); Low-frequency (popmax 1.52%, afr).

How common is SEC24C p.Pro255Ala (c.763C>G) in the general population?

SEC24C p.Pro255Ala (c.763C>G) is low-frequency (popmax 1.52%, afr) (gnomAD).

What do computational predictors say about SEC24C p.Pro255Ala (c.763C>G)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

SEC24C p.Pro255Ala

c.763C>G · rs150235476 · VCV718500

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.72	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 1.4	GERP 0.84, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 14 kb · p 0.5 · regional, not allelic
Overall
CADD	18.91	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.52% African / African-American · 1,144/75,042 alleles

Filtering AF 1.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.42%

Overall 0.0775% 1,250/1,613,514 alleles · low-frequency exomes 606/1,461,210 · genomes 644/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.52%	66
Admixed American	0.09%	1,112
Remaining individualsnot grpmax-eligible	0.0704%	1,420
Middle Eastern	0.033%	3,031
South Asian	0.00329%	30,361
European (non-Finnish)	0.000254%	393,331

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: SEC24C
Protein: p.Pro255Ala
Coding: c.763C>G
MANE Select: NM_198597
dbSNP: rs150235476
Type: single nucleotide variant
Location: chr10:73760299 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.29 · 3 PDB
Residue 255: the 'disordered' region

Full SEC24C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC24C c.1800-7T>C Benign ★★ same type
SEC24C c.3145-4G>A Benign ★★ same type
SEC24C c.850+10T>G Benign ★★ same type
SEC24C p.Ala566= Benign ★★ same type
SEC24C p.Gly257= Benign/Likely benign ★★ same type
SEC24C p.Pro958= Likely benign ★★ same type
SEC24C p.Thr870= Likely benign ★★ same type
SEC24C p.Ala43Val Uncertain significance ★ ⚠ 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/sec24c-p-pro255ala (accessed [today's date]).

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