Is F10 p.Pro331Leu (c.992C>T) pathogenic?

F10 p.Pro331Leu (c.992C>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-30). AlphaMissense: likely pathogenic (0.5926); Absent from gnomAD v4.1.

How common is F10 p.Pro331Leu (c.992C>T) in the general population?

F10 p.Pro331Leu (c.992C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F10 p.Pro331Leu (c.992C>T)?

AlphaMissense predicts likely pathogenic (score 0.5926) — an in-silico prediction, not a clinical call.

F10 p.Pro331Leu

c.992C>T · rs2138557206 · VCV1305191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5926 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5926	likely pathogenic
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -13.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: F10
Protein: p.Pro331Leu
Coding: c.992C>T
MANE Select: NM_000504
dbSNP: rs2138557206
Type: single nucleotide variant
Location: chr13:113149042 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 331: the peptidase s1 domain; an α-helix; a disulfide bond

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F10 p.Pro331= Likely benign ★ same residue
F10 p.Glu54Gly Likely pathogenic ★★ ⚠ same type
F10 p.Gly21Arg Pathogenic ★★ ⚠ same type
F10 p.Gly363Ser Likely pathogenic ★★ same type
F10 p.Gly450Arg Likely pathogenic ★★ same type
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same type
F10 p.Glu268Lys Uncertain significance ★★ ⚠ same type
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same type

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-pro331leu (accessed [today's date]).

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