Is F7 p.Leu208Phe (c.624G>T) pathogenic?

F7 p.Leu208Phe (c.624G>T) is classified Uncertain significance in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: ambiguous (0.3753); Ultra-rare (popmax 0.02%, amr); Associated with Inborn genetic diseases.

What condition is associated with F7 p.Leu208Phe (c.624G>T)?

F7 p.Leu208Phe (c.624G>T) is associated with Inborn genetic diseases (ClinVar).

How common is F7 p.Leu208Phe (c.624G>T) in the general population?

F7 p.Leu208Phe (c.624G>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about F7 p.Leu208Phe (c.624G>T)?

AlphaMissense predicts ambiguous (score 0.3753) — an in-silico prediction, not a clinical call.

F7 p.Leu208Phe

c.624G>T · VCV4252387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3753 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3753	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -7.52	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.22 · regional, not allelic
Overall
CADD	18.33	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 L230F vs ClinVar L208F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,006 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000929% 15/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,001
South Asian	0.0022%	45,541
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Leu208Phe
Coding: c.624G>T
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113117481 (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 208: a disulfide bond

Full F7 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

F7 p.Arg434His Uncertain significance ★★ ⚠ same condition
F7 p.Asp234Asn Uncertain significance ★★ ⚠ same condition
F7 p.Cys232Ser Uncertain significance ★★ ⚠ same condition
F7 p.Glu27Lys Uncertain significance ★★ ⚠ same condition
F7 p.His30Tyr Uncertain significance ★★ ⚠ same condition
F7 p.Lys147Arg Uncertain significance ★★ ⚠ same condition
F7 p.Thr345Ser Uncertain significance ★★ ⚠ same condition
F7 p.Trp225Cys 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/f7-p-leu208phe (accessed [today's date]).

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