Is CFD p.Arg232Cys (c.694C>T) pathogenic?

CFD p.Arg232Cys (c.694C>T) is classified Conflicting classifications of pathogenicity in CFD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.6924); Rare (popmax 0.387%, sas).

How common is CFD p.Arg232Cys (c.694C>T) in the general population?

CFD p.Arg232Cys (c.694C>T) is rare (popmax 0.387%, sas) (gnomAD).

What do computational predictors say about CFD p.Arg232Cys (c.694C>T)?

AlphaMissense predicts likely pathogenic (score 0.6924) — an in-silico prediction, not a clinical call.

CFD p.Arg232Cys

c.694C>T · rs564333282 · VCV761363

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6924 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.387%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6924	likely pathogenic
REVEL	0.462	indeterminate
SaProt	LLR -10.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -2.6
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.387% South Asian · 320/82,738 alleles

Filtering AF 0.352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.338%

Overall 0.0245% 369/1,504,286 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.387%	259
Middle Eastern	0.017%	5,884
Remaining individualsnot grpmax-eligible	0.0135%	7,414
African / African-American	0.00937%	10,678
Admixed American	0.00849%	11,780
European (non-Finnish)	0.00265%	37,764

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.Arg232Cys
Coding: c.694C>T
MANE Select: NM_001928
dbSNP: rs564333282
Type: single nucleotide variant
Location: chr19:863170 (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 232: the peptidase s1 domain; a β-strand

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

Similar variants

CFD p.Arg232His Uncertain significance ★ ⚠ same residue
CFD p.Arg232Pro Uncertain significance ★ ⚠ same residue
CFD p.Arg232= Likely benign ★ 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

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-arg232cys (accessed [today's date]).

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