Is F7 p.Val196Ala (c.587T>C) pathogenic?

F7 p.Val196Ala (c.587T>C) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1091); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with F7 p.Val196Ala (c.587T>C)?

F7 p.Val196Ala (c.587T>C) is associated with Inborn genetic diseases (ClinVar).

How common is F7 p.Val196Ala (c.587T>C) in the general population?

F7 p.Val196Ala (c.587T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about F7 p.Val196Ala (c.587T>C)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

F7 p.Val196Ala

c.587T>C · rs953184897 · VCV2476325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor gain, 28 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.22	GERP -0.72, phastCons 0.16
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	14.15	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V218A vs ClinVar V196A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,952 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,578 alleles · very rare

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: F7
Protein: p.Val196Ala
Coding: c.587T>C
MANE Select: NM_019616
dbSNP: rs953184897
Type: single nucleotide variant
Location: chr13:113116847 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 196: a disulfide bond

Full F7 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

F7 p.Val196Met Uncertain significance ★★ ⚠ same residue
F7 p.Arg434His Uncertain significance ★★ ⚠ same condition
F7 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
F7 p.Cys232Ser Uncertain significance ★★ ⚠ same condition
F7 p.Glu27Lys Uncertain significance ★★ ⚠ same condition
F7 p.His30Tyr Uncertain significance ★★ ⚠ same condition
F7 p.Lys147Arg Uncertain significance ★★ ⚠ same condition
F7 p.Thr345Ser 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/f7-p-val196ala (accessed [today's date]).

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