Is F7 p.Cys60Phe (c.179G>T) pathogenic?

F7 p.Cys60Phe (c.179G>T) is classified Likely pathogenic in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely pathogenic (0.9546); Very rare (popmax 0.000608%, nfe).

How common is F7 p.Cys60Phe (c.179G>T) in the general population?

F7 p.Cys60Phe (c.179G>T) is very rare (popmax 0.000608%, nfe) (gnomAD).

What do computational predictors say about F7 p.Cys60Phe (c.179G>T)?

AlphaMissense predicts likely pathogenic (score 0.9546) — an in-silico prediction, not a clinical call.

F7 p.Cys60Phe

c.179G>T · rs1448296564 · VCV2582790

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000608%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9546	likely pathogenic ✓ concordant with ClinVar · top 7% in F7
REVEL	0.885	moderately pathogenic-leaning
SaProt	LLR -12.50	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	28.7	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 C82F vs ClinVar C60F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000608% European (non-Finnish) · 7/1,151,334 alleles

Filtering AF 0.000253% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000449% 7/1,557,414 alleles · very rare

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.Cys60Phe
Coding: c.179G>T
MANE Select: NM_019616
dbSNP: rs1448296564
Type: single nucleotide variant
Location: chr13:113110804 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB

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

Similar variants

F7 p.Cys60Arg Pathogenic/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-cys60phe (accessed [today's date]).

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