Is F10 p.Ile397Val (c.1189A>G) pathogenic?

F10 p.Ile397Val (c.1189A>G) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-27). AlphaMissense: likely benign (0.0605); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with F10 p.Ile397Val (c.1189A>G)?

F10 p.Ile397Val (c.1189A>G) is associated with Inborn genetic diseases (ClinVar).

How common is F10 p.Ile397Val (c.1189A>G) in the general population?

F10 p.Ile397Val (c.1189A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about F10 p.Ile397Val (c.1189A>G)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

F10 p.Ile397Val

c.1189A>G · VCV3276921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -5.69	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 -0.82	GERP -3.8
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	0.246	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 0.00133% African / African-American · 1/74,928 alleles

Overall 6.2e-05% 1/1,613,076 alleles · very rare exomes 0/1,460,888 · genomes 1/152,188 · joint denominator

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: F10
Protein: p.Ile397Val
Coding: c.1189A>G
MANE Select: NM_000504
Type: single nucleotide variant
Location: chr13:113149239 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 397: the peptidase s1 domain; an α-helix

Full F10 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

F10 p.Glu268Lys Uncertain significance ★★ ⚠ same condition
F10 p.Ala185Asp Uncertain significance ★ ⚠ same condition
F10 p.Ala250Val Uncertain significance ★ same condition
F10 p.Ala457Thr Uncertain significance ★ ⚠ same condition
F10 p.Arg180Gly Uncertain significance ★ ⚠ same condition
F10 p.Arg28Thr Uncertain significance ★ ⚠ same condition
F10 p.Asn97Lys Uncertain significance ★ same condition
F10 p.Asp159Asn 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/f10-p-ile397val (accessed [today's date]).

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