Is F7 p.Pro341His (c.1022C>A) pathogenic?

F7 p.Pro341His (c.1022C>A) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely pathogenic (0.866); Absent from gnomAD v4.1.

How common is F7 p.Pro341His (c.1022C>A) in the general population?

F7 p.Pro341His (c.1022C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F7 p.Pro341His (c.1022C>A)?

AlphaMissense predicts likely pathogenic (score 0.866) — an in-silico prediction, not a clinical call.

F7 p.Pro341His

c.1022C>A · VCV3911970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.866 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.866	likely pathogenic
REVEL	0.847	moderately pathogenic-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.42, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P363H vs ClinVar P341H) — verify the residue.

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: F7
Protein: p.Pro341His
Coding: c.1022C>A
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113118695 (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 341: a UniProt-annotated variant site (in fa7d); a β-strand; the peptidase s1 domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F7 p.Pro341Arg Likely pathogenic ★ same residue
F7 c.225+1G>C Pathogenic ★★ same type
F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.365-2A>G Likely pathogenic ★★ same type
F7 c.505+78G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same type
F7 c.64+5G>A Pathogenic/Likely pathogenic ★★ same type
F7 c.739+1G>A Pathogenic/Likely pathogenic ★★ 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/f7-p-pro341his (accessed [today's date]).

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