Is F5 p.Arg341His (c.1022G>A) pathogenic?

F5 p.Arg341His (c.1022G>A) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-17). AlphaMissense: likely benign (0.2018); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Arg341His (c.1022G>A)?

F5 p.Arg341His (c.1022G>A) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Arg341His (c.1022G>A) in the general population?

F5 p.Arg341His (c.1022G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about F5 p.Arg341His (c.1022G>A)?

AlphaMissense predicts likely benign (score 0.2018) — an in-silico prediction, not a clinical call.

F5 p.Arg341His

c.1022G>A · VCV4870743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2018 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2018	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -7.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -4.2, phastCons 0.01
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	16.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,988 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,922 alleles · very rare exomes 8/1,461,840 · genomes 1/152,082 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,994
Finnishnot grpmax-eligible	0.00156%	64,028
African / African-American	0.00134%	74,880
European (non-Finnish)	0.000424%	235,998

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.Arg341His
Coding: c.1022G>A
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169555278 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 341: a turn

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.Arg341Cys Conflicting classifications of pathogenicity ★ same residue
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

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-arg341his (accessed [today's date]).

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