Is F10 p.Arg27His (c.80G>A) pathogenic?

F10 p.Arg27His (c.80G>A) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely benign (0.0805); Very rare (popmax 0.00333%, amr); Associated with factor X deficiency.

What condition is associated with F10 p.Arg27His (c.80G>A)?

F10 p.Arg27His (c.80G>A) is associated with factor X deficiency (ClinVar).

How common is F10 p.Arg27His (c.80G>A) in the general population?

F10 p.Arg27His (c.80G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about F10 p.Arg27His (c.80G>A)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

F10 p.Arg27His

c.80G>A · rs1263735827 · VCV1098452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -4.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.83	GERP -3.8
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.36 · regional, not allelic
Overall
CADD	3.024	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,998 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,680 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,999
Remaining individualsnot grpmax-eligible	0.0032%	31,231
South Asian	0.0022%	45,523
European (non-Finnish)	0.000169%	590,009

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: F10
Protein: p.Arg27His
Coding: c.80G>A
MANE Select: NM_000504
dbSNP: rs1263735827
Type: single nucleotide variant
Location: chr13:113129461 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly21Arg Pathogenic ★★ ⚠ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu69Lys Likely pathogenic ★ same condition
F10 p.Thr358Met Likely pathogenic ★ ⚠ same condition
F10 p.Asp463His Uncertain significance ★ ⚠ same condition
F10 p.Cys277Ser Uncertain significance ★ ⚠ same condition
F10 p.Glu142Lys Conflicting classifications of pathogenicity ★ ⚠ 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/f10-p-arg27his (accessed [today's date]).

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