Is SEC61A1 p.Phe461= (c.1383C>T) pathogenic?

SEC61A1 p.Phe461= (c.1383C>T) is classified Likely benign in SEC61A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Ultra-rare (popmax 0.035%, amr).

How common is SEC61A1 p.Phe461= (c.1383C>T) in the general population?

SEC61A1 p.Phe461= (c.1383C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

SEC61A1 p.Phe461=

c.1383C>T · rs781266676 · VCV1533159

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4	GERP -4
Overall
CADD	8.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/59,996 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.0018% 29/1,614,036 alleles · ultra-rare exomes 24/1,461,850 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
African / African-American	0.00267%	37,467
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,080
European (non-Finnish)	0.000339%	295,012

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: SEC61A1
Protein: p.Phe461=
Coding: c.1383C>T
MANE Select: NM_013336
dbSNP: rs781266676
Type: single nucleotide variant
Location: chr3:128069614 (GRCh38)

Full SEC61A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/sec61a1-p-phe461 (accessed [today's date]).

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