Is CFD p.Arg137His (c.410G>A) pathogenic?

CFD p.Arg137His (c.410G>A) is classified Uncertain significance in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-18). AlphaMissense: likely benign (0.1439); Very rare (popmax 0.00401%, afr).

How common is CFD p.Arg137His (c.410G>A) in the general population?

CFD p.Arg137His (c.410G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CFD p.Arg137His (c.410G>A)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

CFD p.Arg137His

c.410G>A · rs749867848 · VCV1461173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -10.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP -3.1, phastCons 0.001
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	17.25	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 0.00401% African / African-American · 3/74,758 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000685% 11/1,605,250 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,919
Remaining individualsnot grpmax-eligible	0.00161%	62,152
European (non-Finnish)	0.000594%	168,306

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.Arg137His
Coding: c.410G>A
MANE Select: NM_001928
dbSNP: rs749867848
Type: single nucleotide variant
Location: chr19:861751 (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 137: the peptidase s1 domain

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

Similar variants

CFD p.Arg137Cys Uncertain significance ★★ ⚠ same residue
CFD p.Arg137= 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
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-arg137his (accessed [today's date]).

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