Is F5 p.Ser1705Arg (c.5113A>C) pathogenic?

F5 p.Ser1705Arg (c.5113A>C) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). AlphaMissense: likely pathogenic (0.6053); Very rare (popmax 0.00446%, eas).

How common is F5 p.Ser1705Arg (c.5113A>C) in the general population?

F5 p.Ser1705Arg (c.5113A>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about F5 p.Ser1705Arg (c.5113A>C)?

AlphaMissense predicts likely pathogenic (score 0.6053) — an in-silico prediction, not a clinical call.

F5 p.Ser1705Arg

c.5113A>C · VCV3366752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6053	likely pathogenic
REVEL	0.496	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.84	unconstrained · MANE · 26 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	23.6	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 0.00446% East Asian · 2/44,878 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,660 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: F5
Protein: p.Ser1705Arg
Coding: c.5113A>C
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169530881 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1705: a β-strand; the f5/8 type a 3 domain; the plastocyanin-like 5 domain

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same type
F5 p.Arg1030Ter Pathogenic ★★ same type
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same type
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same type
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same type
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same type
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same type
F5 p.Asp96His 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/f5-p-ser1705arg (accessed [today's date]).

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