Is CFP p.Pro15Leu (c.44C>T) pathogenic?

CFP p.Pro15Leu (c.44C>T) is classified Uncertain significance in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-26). AlphaMissense: likely benign (0.0654); Ultra-rare (popmax 0.0241%, mid).

How common is CFP p.Pro15Leu (c.44C>T) in the general population?

CFP p.Pro15Leu (c.44C>T) is ultra-rare (popmax 0.0241%, mid) (gnomAD).

What do computational predictors say about CFP p.Pro15Leu (c.44C>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

CFP p.Pro15Leu

c.44C>T · rs1427476310 · VCV1966614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -2.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP -2.4, phastCons 0.005
Regional constraint	o/e 0.79	unconstrained · MANE · 5,566 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	0.657	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 0.0241% Middle Eastern · 1/4,148 alleles

Overall 0.000189% 2/1,055,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0241%	4,148
Remaining individualsnot grpmax-eligible	0.00218%	45,938

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.Pro15Leu
Coding: c.44C>T
MANE Select: NM_001145252
dbSNP: rs1427476310
Type: single nucleotide variant
Location: chrX:47629801 (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.Pro15= Likely benign ★ same residue
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

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-pro15leu (accessed [today's date]).

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