Is F7 p.Ser307Pro (c.919T>C) pathogenic?

F7 p.Ser307Pro (c.919T>C) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-10). AlphaMissense: likely pathogenic (0.7333); Very rare (popmax 8.48e-05%, nfe).

How common is F7 p.Ser307Pro (c.919T>C) in the general population?

F7 p.Ser307Pro (c.919T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about F7 p.Ser307Pro (c.919T>C)?

AlphaMissense predicts likely pathogenic (score 0.7333) — an in-silico prediction, not a clinical call.

F7 p.Ser307Pro

c.919T>C · VCV3895751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7333	likely pathogenic
REVEL	0.627	indeterminate
SaProt	LLR -11.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -2.1, phastCons 0.088
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	17.68	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S329P vs ClinVar S307P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,912 alleles

Overall 6.2e-05% 1/1,612,894 alleles · very rare exomes 1/1,460,580 · genomes 0/152,314 · 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: F7
Protein: p.Ser307Pro
Coding: c.919T>C
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113118592 (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 329 UniProt numbering: an α-helix; the peptidase s1 domain

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

Similar variants

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
F7 c.-30A>C 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-ser307pro (accessed [today's date]).

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