Is CFD p.Trp247Ser (c.740G>C) pathogenic?

CFD p.Trp247Ser (c.740G>C) is classified Uncertain significance in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely pathogenic (0.9484); Very rare (popmax 0.00542%, afr).

How common is CFD p.Trp247Ser (c.740G>C) in the general population?

CFD p.Trp247Ser (c.740G>C) is very rare (popmax 0.00542%, afr) (gnomAD).

What do computational predictors say about CFD p.Trp247Ser (c.740G>C)?

AlphaMissense predicts likely pathogenic (score 0.9484) — an in-silico prediction, not a clinical call.

CFD p.Trp247Ser

c.740G>C · rs1165648866 · VCV3143781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00542%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9484	likely pathogenic · top 9% in CFD
REVEL	0.805	moderately pathogenic-leaning
SaProt	LLR -16.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00542% African / African-American · 4/73,758 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.000259% 4/1,544,472 alleles · very rare

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: CFD
Protein: p.Trp247Ser
Coding: c.740G>C
MANE Select: NM_001928
dbSNP: rs1165648866
Type: single nucleotide variant
Location: chr19:863216 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.19 · 40 PDB
Residue 247: the peptidase s1 domain; an α-helix

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

Similar variants

CFD p.Trp247Cys Uncertain significance ★ ⚠ same residue
CFD p.Trp247Leu Uncertain significance ★ ⚠ same residue
CFD c.212+2T>G Likely pathogenic ★★ same type
CFD c.56-1G>C Likely pathogenic ★★ same type
CFD p.Tyr95Ter Pathogenic ★★ same type
ELANE p.Gly203Arg Pathogenic ★★ same type
ELANE p.Ser126Leu Pathogenic ★★ ⚠ same type
CFD p.Ala100Pro 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/cfd-p-trp247ser (accessed [today's date]).

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