Is F5 p.Cys329Phe (c.986G>T) pathogenic?

F5 p.Cys329Phe (c.986G>T) is classified Uncertain significance in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.7919); Ultra-rare (popmax 0.0296%, sas); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Cys329Phe (c.986G>T)?

F5 p.Cys329Phe (c.986G>T) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Cys329Phe (c.986G>T) in the general population?

F5 p.Cys329Phe (c.986G>T) is ultra-rare (popmax 0.0296%, sas) (gnomAD).

How is Congenital factor V deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F5 p.Cys329Phe (c.986G>T)?

AlphaMissense predicts likely pathogenic (score 0.7919) — an in-silico prediction, not a clinical call.

F5 p.Cys329Phe

c.986G>T · VCV4751019

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.7919	likely pathogenic
REVEL	0.904	moderately pathogenic-leaning
SaProt	LLR -14.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0296% South Asian · 27/91,082 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00192% 31/1,614,028 alleles · ultra-rare exomes 28/1,461,834 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0296%	3,373
Remaining individualsnot grpmax-eligible	0.0064%	15,626

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.Cys329Phe
Coding: c.986G>T
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169555314 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 329: a disulfide bond; the f5/8 type a 1 domain; the plastocyanin-like 2 domain

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

Disease context

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

For Congenital factor V deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F5 p.Cys329Ter Pathogenic ★ same residue
F5 p.Cys329Tyr Uncertain significance ⚠ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ 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-cys329phe (accessed [today's date]).

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