Is F10 p.Leu35Pro (c.104T>C) pathogenic?

F10 p.Leu35Pro (c.104T>C) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.3658); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F10 p.Leu35Pro (c.104T>C)?

F10 p.Leu35Pro (c.104T>C) is associated with Inborn genetic diseases (ClinVar).

How common is F10 p.Leu35Pro (c.104T>C) in the general population?

F10 p.Leu35Pro (c.104T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F10 p.Leu35Pro (c.104T>C)?

AlphaMissense predicts ambiguous (score 0.3658) — an in-silico prediction, not a clinical call.

F10 p.Leu35Pro

c.104T>C · VCV3846975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3658	ambiguous
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -14.19	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.36 · regional, not allelic
Overall
CADD	24.6	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

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.Leu35Pro
Coding: c.104T>C
MANE Select: NM_000504
Type: single nucleotide variant
Location: chr13:113129485 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB

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-leu35pro (accessed [today's date]).

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