Is SEC62 p.Ala94= (c.282C>G) pathogenic?

SEC62 p.Ala94= (c.282C>G) is classified Benign in SEC62 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). Common (popmax 6.34%, afr) — too common for a highly-penetrant pathogenic allele.

SEC62 p.Ala94=

Q: How common is SEC62 p.Ala94= (c.282C>G) in the general population?

SEC62 p.Ala94= (c.282C>G) is common (popmax 6.34%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.282C>G · rs35176867 · VCV775924

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.34%, afr) — too common for a highly-penetrant pathogenic allele

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 0.16	GERP -2.5, phastCons 0.36
Overall
CADD	2.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.34% African / African-American · 4,676/73,702 alleles

Filtering AF 6.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.13%

Overall 0.325% 5,211/1,604,808 alleles · common exomes 2,589/1,455,870 · genomes 2,622/148,938 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.34%	16
Remaining individualsnot grpmax-eligible	0.438%	228
Admixed American	0.298%	335
Middle Eastern	0.183%	548
South Asian	0.0188%	5,310
European (non-Finnish)	0.00485%	20,627
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,388

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: SEC62
Protein: p.Ala94=
Coding: c.282C>G
MANE Select: NM_003262
dbSNP: rs35176867
Type: single nucleotide variant
Location: chr3:169982737 (GRCh38)
Gene constraint: LOEUF 0.392 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.29 · 1 PDB

Full SEC62 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEC62 p.Ala94Val Uncertain significance ★ ⚠ same residue
SEC62 p.Ala25= Benign ★★ same type
SEC62 p.Ala115Asp Uncertain significance ★ ⚠ same type
SEC62 p.Ala209Val Uncertain significance ★ same type
SEC62 p.Arg339Gln Uncertain significance ★ ⚠ same type
SEC62 p.Arg347Gly Uncertain significance ★ ⚠ same type
SEC62 p.Asn129Tyr Uncertain significance ★ ⚠ same type
SEC62 p.Glu116Gly 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/sec62-p-ala94 (accessed [today's date]).

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