Is CFP p.Ser40= (c.120C>T) pathogenic?

CFP p.Ser40= (c.120C>T) is classified Likely benign in CFP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-22). Very rare (popmax 0.00309%, eas).

How common is CFP p.Ser40= (c.120C>T) in the general population?

CFP p.Ser40= (c.120C>T) is very rare (popmax 0.00309%, eas) (gnomAD).

CFP p.Ser40=

c.120C>T · rs763653323 · VCV1662948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00309%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.6	GERP -3.2
Overall
CADD	0.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00309% East Asian · 1/32,380 alleles

Overall 0.000283% 3/1,061,101 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00309%	32,380
Admixed American	0.00255%	39,139
European (non-Finnish)	0.000114%	875,672

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.Ser40=
Coding: c.120C>T
MANE Select: NM_001145252
dbSNP: rs763653323
Type: single nucleotide variant
Location: chrX:47629631 (GRCh38)
Structure: AlphaFold pLDDT 83.75 · 14 PDB
Residue 40: the tsp type-1 0 domain; a disulfide bond; a β-strand

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

Similar variants

CFP p.Ser40Pro Uncertain significance ★ ⚠ 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-ser40 (accessed [today's date]).

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