Is CFP p.Arg100Gln (c.299G>A) pathogenic?

CFP p.Arg100Gln (c.299G>A) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.1213); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFP p.Arg100Gln (c.299G>A)?

CFP p.Arg100Gln (c.299G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CFP p.Arg100Gln (c.299G>A) in the general population?

CFP p.Arg100Gln (c.299G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about CFP p.Arg100Gln (c.299G>A)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

CFP p.Arg100Gln

c.299G>A · VCV3832527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.803	moderately pathogenic-leaning
SaProt	LLR -11.37	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	23.9	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 0.00296% East Asian · 1/33,749 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000248% 3/1,209,480 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,749
European (non-Finnish)	0.000223%	447,497

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: CFP
Protein: p.Arg100Gln
Coding: c.299G>A
MANE Select: NM_001145252
Type: single nucleotide variant
Location: chrX:47628206 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 100: the tsp type-1 1 domain; a disulfide bond; a UniProt-annotated variant site (in pfd; type ii); a β-strand

Full CFP 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

CFP p.Arg100Trp Uncertain significance ★ ⚠ same residue
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same condition
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same condition
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same condition
CFP p.Asn307Ser Uncertain significance ★★ ⚠ same condition
CFP p.Glu215Lys Uncertain significance ★★ ⚠ same condition
CFP p.Gly200Asp Uncertain significance ★★ ⚠ same condition
CFP p.Lys413Glu 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/cfp-p-arg100gln (accessed [today's date]).

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