Is F5 p.Phe604Val (c.1810T>G) pathogenic?

F5 p.Phe604Val (c.1810T>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: ambiguous (0.4743); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Phe604Val (c.1810T>G)?

F5 p.Phe604Val (c.1810T>G) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Phe604Val (c.1810T>G) in the general population?

F5 p.Phe604Val (c.1810T>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about F5 p.Phe604Val (c.1810T>G)?

AlphaMissense predicts ambiguous (score 0.4743) — an in-silico prediction, not a clinical call.

F5 p.Phe604Val

c.1810T>G · rs1361894720 · VCV3230344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4743	ambiguous
REVEL	0.554	indeterminate
SaProt	LLR -2.36	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.73, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	20.9	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 0.000678% European (non-Finnish) · 8/1,180,028 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,054 alleles · very rare exomes 7/1,461,804 · genomes 1/152,250 · 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: F5
Protein: p.Phe604Val
Coding: c.1810T>G
MANE Select: NM_000130
dbSNP: rs1361894720
Type: single nucleotide variant
Location: chr1:169544461 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 604: the plastocyanin-like 4 domain; a β-strand; the f5/8 type a 2 domain

Full F5 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

F5 p.Arg441His Uncertain significance ★★ ⚠ same condition
F5 p.Asn1559Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asn1575Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asp1739Gly Uncertain significance ★★ ⚠ same condition
F5 p.Glu2029Asp Uncertain significance ★★ ⚠ same condition
F5 p.Glu48Gln Uncertain significance ★★ ⚠ same condition
F5 p.His812Tyr Uncertain significance ★★ ⚠ same condition
F5 p.Ile1558Val 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/f5-p-phe604val (accessed [today's date]).

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