Is F8 p.Arg602Gln (c.1805G>A) pathogenic?

F8 p.Arg602Gln (c.1805G>A) is classified Likely benign in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). AlphaMissense: likely benign (0.0583); Very rare (popmax 0.00425%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F8 p.Arg602Gln (c.1805G>A)?

F8 p.Arg602Gln (c.1805G>A) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Arg602Gln (c.1805G>A) in the general population?

F8 p.Arg602Gln (c.1805G>A) is very rare (popmax 0.00425%, nfe) (gnomAD).

What do computational predictors say about F8 p.Arg602Gln (c.1805G>A)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

F8 p.Arg602Gln

c.1805G>A · rs782241116 · VCV3091487

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00425%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -4.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.7
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00425% European (non-Finnish) · 38/894,430 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00339% 41/1,209,094 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00425%	23,538
Remaining individualsnot grpmax-eligible	0.00421%	23,778
Finnishnot grpmax-eligible	0.00215%	46,547

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: F8
Protein: p.Arg602Gln
Coding: c.1805G>A
MANE Select: NM_000132
dbSNP: rs782241116
Type: single nucleotide variant
Location: chrX:154953990 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 602: the plastocyanin-like 4 domain; a UniProt-annotated variant site (in hema; mild familial); an α-helix; the f5/8 type a 2 domain

Full F8 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

F8 p.Arg602Ter Pathogenic ★★★ same residue
F8 p.Arg602Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
F8 p.Tyr1699Phe Pathogenic ★★ ⚠ same condition
F8 p.Ala2108Val Uncertain significance ★★ ⚠ same condition
F8 p.Gln1049Lys Uncertain significance ★★ ⚠ same condition
F8 p.Gln1209Arg Uncertain significance ★★ ⚠ same condition
F8 p.Gly1729Trp Uncertain significance ★★ ⚠ same condition
F8 p.Leu13Phe 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/f8-p-arg602gln (accessed [today's date]).

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