Is F7 p.Phe62Ser (c.185T>C) pathogenic?

F7 p.Phe62Ser (c.185T>C) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: ambiguous (0.4415); Very rare (popmax 7.11e-05%).

How common is F7 p.Phe62Ser (c.185T>C) in the general population?

F7 p.Phe62Ser (c.185T>C) is very rare (popmax 7.11e-05%) (gnomAD).

What do computational predictors say about F7 p.Phe62Ser (c.185T>C)?

AlphaMissense predicts ambiguous (score 0.4415) — an in-silico prediction, not a clinical call.

F7 p.Phe62Ser

c.185T>C · rs2036077301 · VCV2573369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4415 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.11e-05%)

Computational evidence

Protein change
AlphaMissense	0.4415	ambiguous
REVEL	0.492	indeterminate
SaProt	LLR -10.99	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -3.6, phastCons 0.98
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	23.8	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 F84S vs ClinVar F62S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.11e-05%

Overall 7.11e-05% 1/1,406,426 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.Phe62Ser
Coding: c.185T>C
MANE Select: NM_019616
dbSNP: rs2036077301
Type: single nucleotide variant
Location: chr13:113110810 (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 62: the gla 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-phe62ser (accessed [today's date]).

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