Is CFD p.Ter254Tyr (c.762G>C) pathogenic?

CFD p.Ter254Tyr (c.762G>C) is classified Uncertain significance in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). Very rare (popmax 0.00236%, sas).

How common is CFD p.Ter254Tyr (c.762G>C) in the general population?

CFD p.Ter254Tyr (c.762G>C) is very rare (popmax 0.00236%, sas) (gnomAD).

CFD p.Ter254Tyr

c.762G>C · rs868017405 · VCV1354292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00236%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.28	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.078	GERP -4
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00236% South Asian · 2/84,694 alleles

Filtering AF 0.000392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000147%

Overall 0.000502% 7/1,394,986 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00236%	42,347
Admixed American	0.00194%	51,558
European (non-Finnish)	0.000347%	288,249

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.Ter254Tyr
Coding: c.762G>C
MANE Select: NM_001928
dbSNP: rs868017405
Type: single nucleotide variant
Location: chr19:863238 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.19 · 40 PDB

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-ter254tyr (accessed [today's date]).

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