Is CFD p.Gly210Ala (c.629G>C) pathogenic?

CFD p.Gly210Ala (c.629G>C) is classified Uncertain significance in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely pathogenic (0.6175); Ultra-rare (popmax 0.0546%, mid).

How common is CFD p.Gly210Ala (c.629G>C) in the general population?

CFD p.Gly210Ala (c.629G>C) is ultra-rare (popmax 0.0546%, mid) (gnomAD).

What do computational predictors say about CFD p.Gly210Ala (c.629G>C)?

AlphaMissense predicts likely pathogenic (score 0.6175) — an in-silico prediction, not a clinical call.

CFD p.Gly210Ala

c.629G>C · rs781602858 · VCV1466181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6175 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6175	likely pathogenic
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -10.19	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 2.6, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	26.8	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 0.0546% Middle Eastern · 3/5,494 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.00347% 53/1,525,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0546%	1,831
East Asian	0.0296%	3,379
South Asian	0.0167%	5,982
African / African-American	0.00412%	24,279
Remaining individualsnot grpmax-eligible	0.00337%	29,677
European (non-Finnish)	0.00167%	59,921

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.Gly210Ala
Coding: c.629G>C
MANE Select: NM_001928
dbSNP: rs781602858
Type: single nucleotide variant
Location: chr19:863105 (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 210: a disulfide bond; the peptidase s1 domain

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

Similar variants

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
CFD p.Ala129Thr Uncertain significance ★★ ⚠ same type
CFD p.Ala143Val 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-gly210ala (accessed [today's date]).

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