Is CFP c.227+2T>G pathogenic?

CFP c.227+2T>G is classified Likely pathogenic in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Very rare (popmax 0.00262%, amr).

How common is CFP c.227+2T>G in the general population?

CFP c.227+2T>G is very rare (popmax 0.00262%, amr) (gnomAD).

CFP c.227+2T>G

rs1317275240 · VCV1497106

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00262%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.81	donor loss · deltas
Pangolin	Δ0.78	loss · gain 0.64 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00262% Admixed American · 1/38,142 alleles

Filtering AF 0.000256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.00062% 7/1,128,357 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00262%	38,142
European (non-Finnish)	0.000713%	140,301

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
Coding: c.227+2T>G
MANE Select: NM_001145252
dbSNP: rs1317275240
Type: single nucleotide variant
Location: chrX:47629522 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB

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

Similar variants

CFP p.Trp321Gly Pathogenic ★★ same type
CFP p.Ala402Gly Uncertain significance ★★ ⚠ same type
CFP p.Arg157Gln Uncertain significance ★★ ⚠ same type
CFP p.Arg157Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg159Cys Uncertain significance ★★ ⚠ same type
CFP p.Arg247Trp Uncertain significance ★★ ⚠ same type
CFP p.Arg438Trp Uncertain significance ★★ ⚠ same type
CFP p.Asn307Ser 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/cfp-c-227-plus-2t-g (accessed [today's date]).

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