Is F5 p.Pro1242Arg (c.3725C>G) pathogenic?

F5 p.Pro1242Arg (c.3725C>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.1139); Ultra-rare (popmax 0.0563%, afr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro1242Arg (c.3725C>G)?

F5 p.Pro1242Arg (c.3725C>G) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Pro1242Arg (c.3725C>G) in the general population?

F5 p.Pro1242Arg (c.3725C>G) is ultra-rare (popmax 0.0563%, afr) (gnomAD).

What do computational predictors say about F5 p.Pro1242Arg (c.3725C>G)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

F5 p.Pro1242Arg

c.3725C>G · VCV3847035

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0563%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -12.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.43	GERP 0.56, phastCons 0.002
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	15.58	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 0.0563% African / African-American · 37/65,744 alleles

Filtering AF 0.0419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.037%

Overall 0.00268% 42/1,565,230 alleles · ultra-rare exomes 21/1,439,168 · genomes 21/126,062 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0563%	1,777
Remaining individualsnot grpmax-eligible	0.00663%	15,093
South Asian	0.00112%	89,380

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: F5
Protein: p.Pro1242Arg
Coding: c.3725C>G
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169541365 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1242: the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region

Full F5 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

F5 p.Arg441His Uncertain significance ★★ ⚠ same condition
F5 p.Asn1559Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asn1575Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asp1739Gly Uncertain significance ★★ ⚠ same condition
F5 p.Glu2029Asp Uncertain significance ★★ ⚠ same condition
F5 p.Glu48Gln Uncertain significance ★★ ⚠ same condition
F5 p.His812Tyr Uncertain significance ★★ ⚠ same condition
F5 p.Ile1558Val 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/f5-p-pro1242arg (accessed [today's date]).

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