Is CFD p.Asp96Tyr (c.286G>T) pathogenic?

CFD p.Asp96Tyr (c.286G>T) is classified Uncertain significance in CFD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-27). AlphaMissense: ambiguous (0.3509); Ultra-rare (popmax 0.0429%, sas).

How common is CFD p.Asp96Tyr (c.286G>T) in the general population?

CFD p.Asp96Tyr (c.286G>T) is ultra-rare (popmax 0.0429%, sas) (gnomAD).

What do computational predictors say about CFD p.Asp96Tyr (c.286G>T)?

AlphaMissense predicts ambiguous (score 0.3509) — an in-silico prediction, not a clinical call.

CFD p.Asp96Tyr

c.286G>T · rs758677702 · VCV1493995

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0429%, sas)

Computational evidence

Protein change
AlphaMissense	0.3509	ambiguous
REVEL	0.348	indeterminate
SaProt	LLR -11.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1, phastCons 0.096
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	19.28	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 0.0429% South Asian · 39/90,890 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0285%

Overall 0.00269% 39/1,449,170 alleles · ultra-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.Asp96Tyr
Coding: c.286G>T
MANE Select: NM_001928
dbSNP: rs758677702
Type: single nucleotide variant
Location: chr19:860934 (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 96: the peptidase s1 domain; a β-strand

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-asp96tyr (accessed [today's date]).

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