Is F5 p.Arg2102Cys (c.6304C>T) pathogenic?

F5 p.Arg2102Cys (c.6304C>T) is classified Likely pathogenic in F5 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-02-01). AlphaMissense: likely pathogenic (0.6069); Very rare (popmax 0.00333%, amr); Associated with factor V deficiency.

What condition is associated with F5 p.Arg2102Cys (c.6304C>T)?

F5 p.Arg2102Cys (c.6304C>T) is associated with factor V deficiency (ClinVar).

How common is F5 p.Arg2102Cys (c.6304C>T) in the general population?

F5 p.Arg2102Cys (c.6304C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about F5 p.Arg2102Cys (c.6304C>T)?

AlphaMissense predicts likely pathogenic (score 0.6069) — an in-silico prediction, not a clinical call.

F5 p.Arg2102Cys

c.6304C>T · rs118203910 · VCV654

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6069 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.6069	likely pathogenic ✓ concordant with ClinVar
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 0.81, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 26 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	31.0	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 0.00333% Admixed American · 2/59,990 alleles

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

Overall 0.000753% 11/1,461,556 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
Admixed Americangrpmax	0.00333%	29,995
East Asian	0.00223%	44,866
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,058
European (non-Finnish)	0.000424%	235,955

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg2102Cys
Coding: c.6304C>T
MANE Select: NM_000130
dbSNP: rs118203910
Type: single nucleotide variant
Location: chr1:169518453 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 2102: a disulfide bond; a UniProt-annotated variant site (in fa5d; impairs both factor v secretion and activity); a UniProt-annotated variant site (in thph2); the f5/8 type c 2 domain

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg376Ser 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-arg2102cys (accessed [today's date]).

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