Is F11 p.Ala393= (c.1179G>A) pathogenic?

F11 p.Ala393= (c.1179G>A) is classified Likely benign in F11 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.0333%, amr).

How common is F11 p.Ala393= (c.1179G>A) in the general population?

F11 p.Ala393= (c.1179G>A) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

F11 p.Ala393=

c.1179G>A · rs145927314 · VCV1086753

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.7
Overall
CADD	0.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Admixed American · 20/60,006 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.0193% 312/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Admixed Americangrpmax	0.0333%	3,000
European (non-Finnish)	0.0219%	4,556
Middle Eastern	0.0164%	6,082
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
African / African-American	0.00801%	12,488
South Asian	0.0022%	45,542

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: F11
Protein: p.Ala393=
Coding: c.1179G>A
MANE Select: NM_000128
dbSNP: rs145927314
Type: single nucleotide variant
Location: chr4:186284135 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 393: a β-strand; a disulfide bond; the peptidase s1 domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F11 c.1136-1G>C Likely pathogenic ★★ same type
F11 c.1480+1G>T Likely pathogenic ★★ same type
F11 c.1481-1G>T Likely pathogenic ★★ same type
F11 c.1716+1G>A Pathogenic ★★ same type
F11 c.325+1G>A Pathogenic ★★ same type
F11 c.326-1G>A Pathogenic ★★ same type
F11 c.595+3A>G Pathogenic/Likely pathogenic ★★ same type
F11 c.755+2T>C Pathogenic ★★ 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/f11-p-ala393 (accessed [today's date]).

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