Is F5 p.Pro1496Ala (c.4486C>G) pathogenic?

F5 p.Pro1496Ala (c.4486C>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely benign (0.0772); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro1496Ala (c.4486C>G)?

F5 p.Pro1496Ala (c.4486C>G) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Pro1496Ala (c.4486C>G) in the general population?

F5 p.Pro1496Ala (c.4486C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F5 p.Pro1496Ala (c.4486C>G)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

F5 p.Pro1496Ala

c.4486C>G · VCV4020765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -0.56, phastCons 0.16
Regional constraint	o/e 1.08	unconstrained · MANE · 679 bp · p 0.18 · regional, not allelic
Overall
CADD	9.262	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F5
Protein: p.Pro1496Ala
Coding: c.4486C>G
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169540604 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1496: 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-pro1496ala (accessed [today's date]).

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