Is F11 p.Arg268His (c.803G>A) pathogenic?

F11 p.Arg268His (c.803G>A) is classified Conflicting classifications of pathogenicity in F11 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.012%, afr); Associated with factor XI deficiency.

What condition is associated with F11 p.Arg268His (c.803G>A)?

F11 p.Arg268His (c.803G>A) is associated with factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Arg268His (c.803G>A) in the general population?

F11 p.Arg268His (c.803G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about F11 p.Arg268His (c.803G>A)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

F11 p.Arg268His

c.803G>A · rs201688862 · VCV551022

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.7	GERP -0.72, phastCons 0.94
Overall
CADD	16.79	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 0.012% African / African-American · 9/75,008 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.0018% 29/1,614,066 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,334
Admixed American	0.0117%	8,574
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,074
European (non-Finnish)	0.000932%	107,272

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.Arg268His
Coding: c.803G>A
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs201688862
Type: single nucleotide variant
Location: chr4:186280059 (GRCh38)
Structure: AlphaFold pLDDT 68.98

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

Disease context

factor XI deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital factor XI deficiency

Similar variants

F11 p.Arg268Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 c.865+2T>C Likely pathogenic ★★ same condition
F11 p.Ala109Thr Pathogenic ★★ ⚠ same condition

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-arg268his (accessed [today's date]).

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