Is F5 p.Ile82Val (c.244A>G) pathogenic?

F5 p.Ile82Val (c.244A>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.0769); Very rare (popmax 0.00723%, nfe); Associated with thrombophilia due to activated protein C resistance.

What condition is associated with F5 p.Ile82Val (c.244A>G)?

F5 p.Ile82Val (c.244A>G) is associated with thrombophilia due to activated protein C resistance (ClinVar).

How common is F5 p.Ile82Val (c.244A>G) in the general population?

F5 p.Ile82Val (c.244A>G) is very rare (popmax 0.00723%, nfe) (gnomAD).

What do computational predictors say about F5 p.Ile82Val (c.244A>G)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

F5 p.Ile82Val

c.244A>G · rs377674263 · VCV2572148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00723%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

thrombophilia due to activated protein C resistance

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -4.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	18.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00723% European (non-Finnish) · 79/1,093,104 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00546%

Overall 0.00556% 84/1,511,396 alleles · very rare exomes 77/1,359,172 · genomes 7/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00723%	13,837
Remaining individualsnot grpmax-eligible	0.0051%	19,603
Admixed American	0.00173%	57,760
South Asian	0.00117%	85,484

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.Ile82Val
Coding: c.244A>G
MANE Select: NM_000130
dbSNP: rs377674263
Type: single nucleotide variant
Location: chr1:169582437 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 82: a turn; the f5/8 type a 1 domain; the plastocyanin-like 1 domain

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

Disease context

thrombophilia due to activated protein C resistance — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Ala38Thr Uncertain significance ★★ ⚠ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg376Ser Uncertain significance ★★ ⚠ same condition
F5 p.His1845Arg Uncertain significance ★★ ⚠ same condition
F5 p.Ile2136Thr Uncertain significance ★★ ⚠ same condition
F5 p.Thr1978Ile Uncertain significance ★★ ⚠ same condition
F5 p.Asp2222Gly Benign/Likely benign ★★ 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-ile82val (accessed [today's date]).

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