Is F10 p.Arg327Trp (c.979C>T) pathogenic?

F10 p.Arg327Trp (c.979C>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: likely benign (0.2249); Very rare (popmax 0.00449%, nfe).

How common is F10 p.Arg327Trp (c.979C>T) in the general population?

F10 p.Arg327Trp (c.979C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about F10 p.Arg327Trp (c.979C>T)?

AlphaMissense predicts likely benign (score 0.2249) — an in-silico prediction, not a clinical call.

F10 p.Arg327Trp

c.979C>T · VCV4282353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2249	likely benign
REVEL	0.565	indeterminate
SaProt	LLR -12.70	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.8, phastCons 0.026
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	22.5	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 0.00449% European (non-Finnish) · 53/1,180,030 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.0036% 58/1,613,342 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,265
Admixed American	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00134%	74,884

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.Arg327Trp
Coding: c.979C>T
MANE Select: NM_000504
Type: single nucleotide variant
Location: chr13:113149029 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 327: the peptidase s1 domain; a β-strand; a disulfide bond; a UniProt-annotated variant site (in fa10d)

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

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ same type
F10 p.Gly21Arg Pathogenic ★★ ⚠ same type
F10 p.Gly363Ser Likely pathogenic ★★ same type
F10 p.Gly450Arg Likely pathogenic ★★ same type
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same type
F10 p.Glu268Lys Uncertain significance ★★ ⚠ same type
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same type
F10 p.Gly106= Uncertain significance ★★ 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/f10-p-arg327trp (accessed [today's date]).

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