Is F2 p.Gln33Pro (c.98A>C) pathogenic?

F2 p.Gln33Pro (c.98A>C) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely benign (0.1692); Very rare (popmax 0.000171%, nfe).

How common is F2 p.Gln33Pro (c.98A>C) in the general population?

F2 p.Gln33Pro (c.98A>C) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about F2 p.Gln33Pro (c.98A>C)?

AlphaMissense predicts likely benign (score 0.1692) — an in-silico prediction, not a clinical call.

F2 p.Gln33Pro

c.98A>C · rs1234951610 · VCV806659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1692	likely benign
REVEL	0.526	indeterminate
SaProt	LLR -8.23	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 1.2	GERP -3.5, phastCons 0.97
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	19.39	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 0.000171% European (non-Finnish) · 2/1,171,370 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000126% 2/1,593,474 alleles · very rare exomes 1/1,441,340 · genomes 1/152,134 · 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: F2
Protein: p.Gln33Pro
Coding: c.98A>C
MANE Select: NM_000506
dbSNP: rs1234951610
Type: single nucleotide variant
Location: chr11:46719720 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB

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

Similar variants

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
F2 p.Ala17Ser 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-gln33pro (accessed [today's date]).

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