Is F2 p.Arg383Gln (c.1148G>A) pathogenic?

F2 p.Arg383Gln (c.1148G>A) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely benign (0.0989); Very rare (popmax 0.00401%, afr).

How common is F2 p.Arg383Gln (c.1148G>A) in the general population?

F2 p.Arg383Gln (c.1148G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about F2 p.Arg383Gln (c.1148G>A)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

F2 p.Arg383Gln

c.1148G>A · rs774640288 · VCV2641749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.74, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	25.5	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 0.00401% African / African-American · 3/74,778 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00106% 17/1,610,398 alleles · very rare exomes 15/1,458,410 · genomes 2/151,988 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,926
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,484
Remaining individualsnot grpmax-eligible	0.0016%	62,392
South Asian	0.00111%	90,114
European (non-Finnish)	0.000933%	107,181

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: F2
Protein: p.Arg383Gln
Coding: c.1148G>A
MANE Select: NM_000506
dbSNP: rs774640288
Type: single nucleotide variant
Location: chr11:46728013 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 383: the peptidase s1 domain; a β-strand

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F2 p.Arg383Trp Uncertain significance ★ ⚠ same residue
F2 p.Arg314His Likely pathogenic ★★ ⚠ same type
F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same type
F2 p.Arg500Gln Pathogenic ★★ ⚠ same type
F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same type
F2 p.Arg596Gln Pathogenic ★★ ⚠ same type
F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same type
F2 c.559+5G>A Uncertain significance ★★ 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/f2-p-arg383gln (accessed [today's date]).

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