Is F2 p.Arg35Trp (c.103C>T) pathogenic?

F2 p.Arg35Trp (c.103C>T) is classified Uncertain significance in F2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0878); Ultra-rare (popmax 0.0105%, amr); Associated with Inborn genetic diseases.

What condition is associated with F2 p.Arg35Trp (c.103C>T)?

F2 p.Arg35Trp (c.103C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F2 p.Arg35Trp (c.103C>T) in the general population?

F2 p.Arg35Trp (c.103C>T) is ultra-rare (popmax 0.0105%, amr) (gnomAD).

What do computational predictors say about F2 p.Arg35Trp (c.103C>T)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

F2 p.Arg35Trp

c.103C>T · rs144785536 · VCV2444550

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -10.39	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 -0.015	GERP -0.42
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	16.5	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 0.0105% Admixed American · 6/57,064 alleles

Filtering AF 0.00457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00363%

Overall 0.00445% 71/1,594,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0105%	9,511
European (non-Finnish)	0.00504%	19,860
Remaining individualsnot grpmax-eligible	0.00324%	30,849
African / African-American	0.00268%	37,289
South Asian	0.00229%	43,678

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: F2
Protein: p.Arg35Trp
Coding: c.103C>T
MANE Select: NM_000506
dbSNP: rs144785536
Type: single nucleotide variant
Location: chr11:46719725 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F2 p.Arg35Gln Uncertain significance ★ ⚠ same residue
F2 p.Arg35= Likely benign ★ same residue
F2 p.Ala490Thr Uncertain significance ★★ ⚠ same condition
F2 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
F2 p.Arg224Cys Uncertain significance ★★ ⚠ same condition
F2 p.Ile438Thr Uncertain significance ★★ ⚠ same condition
F2 p.Pro471Thr Uncertain significance ★★ ⚠ same condition
F2 p.Thr488Met Uncertain significance ★★ ⚠ 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/f2-p-arg35trp (accessed [today's date]).

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