Is F11 p.Ser266Asn (c.797G>A) pathogenic?

F11 p.Ser266Asn (c.797G>A) is classified Conflicting classifications of pathogenicity in F11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1147); Rare (popmax 0.235%, afr).

How common is F11 p.Ser266Asn (c.797G>A) in the general population?

F11 p.Ser266Asn (c.797G>A) is rare (popmax 0.235%, afr) (gnomAD).

What do computational predictors say about F11 p.Ser266Asn (c.797G>A)?

AlphaMissense predicts likely benign (score 0.1147) — an in-silico prediction, not a clinical call.

F11 p.Ser266Asn

c.797G>A · rs145168351 · VCV746899

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1147 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.235%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1147	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -6.53	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 2.9	GERP -1.9, phastCons 0.95
Overall
CADD	15.85	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 0.235% African / African-American · 176/75,022 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.013% 210/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.235%	426
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Admixed American	0.005%	20,008
South Asian	0.00329%	30,358
European (non-Finnish)	0.00136%	73,749

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.Ser266Asn
Coding: c.797G>A
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs145168351
Type: single nucleotide variant
Location: chr4:186280053 (GRCh38)
Structure: AlphaFold pLDDT 68.98

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

Similar variants

F11 p.Ser266Gly Uncertain significance ★ ⚠ same residue
F11 p.Ser266Arg Uncertain significance ⚠ same residue
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

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-ser266asn (accessed [today's date]).

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