Is CFP p.Leu18= (c.54G>A) pathogenic?

CFP p.Leu18= (c.54G>A) is classified Likely benign in CFP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-29). Very rare (popmax 0.0038%, sas).

How common is CFP p.Leu18= (c.54G>A) in the general population?

CFP p.Leu18= (c.54G>A) is very rare (popmax 0.0038%, sas) (gnomAD).

CFP p.Leu18=

c.54G>A · rs746716714 · VCV3007652

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0038%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.2
Overall
CADD	1.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0038% South Asian · 2/52,580 alleles

Filtering AF 0.000676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.00111% 13/1,167,236 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0038%	26,290
European (non-Finnish)	0.00126%	79,405

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.Leu18=
Coding: c.54G>A
MANE Select: NM_001145252
dbSNP: rs746716714
Type: single nucleotide variant
Location: chrX:47629791 (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-p-leu18 (accessed [today's date]).

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