Is F5 p.Asp656Glu (c.1968T>A) pathogenic?

F5 p.Asp656Glu (c.1968T>A) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely pathogenic (0.6849); Ultra-rare (popmax 0.0361%, afr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Asp656Glu (c.1968T>A)?

F5 p.Asp656Glu (c.1968T>A) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Asp656Glu (c.1968T>A) in the general population?

F5 p.Asp656Glu (c.1968T>A) is ultra-rare (popmax 0.0361%, afr) (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.Asp656Glu (c.1968T>A)?

AlphaMissense predicts likely pathogenic (score 0.6849) — an in-silico prediction, not a clinical call.

F5 p.Asp656Glu

c.1968T>A · VCV4751627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0361%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.6849	likely pathogenic
REVEL	0.602	indeterminate
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -2.4, phastCons 0.97
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	20.8	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 0.0361% African / African-American · 27/74,886 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00174% 28/1,613,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0361%	2,774
Admixed American	0.00167%	59,988

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.Asp656Glu
Coding: c.1968T>A
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169544303 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 656: the plastocyanin-like 4 domain; a disulfide bond; the f5/8 type a 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

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F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Asp96His 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-asp656glu (accessed [today's date]).

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