Is F11 p.Arg162His (c.485G>A) pathogenic?

F11 p.Arg162His (c.485G>A) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely benign (0.1582); Ultra-rare (popmax 0.0133%, amr).

How common is F11 p.Arg162His (c.485G>A) in the general population?

F11 p.Arg162His (c.485G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about F11 p.Arg162His (c.485G>A)?

AlphaMissense predicts likely benign (score 0.1582) — an in-silico prediction, not a clinical call.

F11 p.Arg162His

c.485G>A · VCV3379573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1582	likely benign
REVEL	0.713	pathogenic-leaning
SaProt	LLR -10.55	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.63	loss · gain 0.22 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.3	GERP 2.4, phastCons 1
Overall
CADD	34.0	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 0.0133% Admixed American · 8/59,998 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00211% 34/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,500
South Asian	0.00329%	30,358
European (non-Finnish)	0.00195%	51,306

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.Arg162His
Coding: c.485G>A
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186274275 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 162: a turn; a disulfide bond; the apple 2 domain

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

Similar variants

F11 p.Arg162Cys Conflicting classifications of pathogenicity ★ ⚠ 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
F11 c.595+3A>G Pathogenic/Likely 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-arg162his (accessed [today's date]).

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