Is F7 p.Arg117Trp (c.349C>T) pathogenic?

F7 p.Arg117Trp (c.349C>T) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.168); Very rare (popmax 0.0022%, sas).

How common is F7 p.Arg117Trp (c.349C>T) in the general population?

F7 p.Arg117Trp (c.349C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about F7 p.Arg117Trp (c.349C>T)?

AlphaMissense predicts likely benign (score 0.168) — an in-silico prediction, not a clinical call.

F7 p.Arg117Trp

c.349C>T · VCV3895931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.168	likely benign
REVEL	0.676	pathogenic-leaning
SaProt	LLR -11.80	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R139W vs ClinVar R117W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000684% 10/1,461,692 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Admixed American	0.00167%	60,026
Finnishnot grpmax-eligible	0.00157%	63,846
European (non-Finnish)	0.000508%	196,671

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: F7
Protein: p.Arg117Trp
Coding: c.349C>T
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113113945 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 117: a turn; a disulfide bond; the egf-like 1; calcium-binding domain; a UniProt-annotated variant site (in fa7d; exhibits no procoagulant activity and is unable to bind tissue factor)

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F7 p.Arg117Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
F7 c.225+1G>C Pathogenic ★★ same type
F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.365-2A>G Likely pathogenic ★★ same type
F7 c.505+78G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same type
F7 c.64+5G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.739+1G>A 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/f7-p-arg117trp (accessed [today's date]).

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