Is CFD p.Val78Ala (c.233T>C) pathogenic?

CFD p.Val78Ala (c.233T>C) is classified Uncertain significance in CFD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-14). AlphaMissense: likely pathogenic (0.6856); Very rare (popmax 0.000427%, nfe).

How common is CFD p.Val78Ala (c.233T>C) in the general population?

CFD p.Val78Ala (c.233T>C) is very rare (popmax 0.000427%, nfe) (gnomAD).

What do computational predictors say about CFD p.Val78Ala (c.233T>C)?

AlphaMissense predicts likely pathogenic (score 0.6856) — an in-silico prediction, not a clinical call.

CFD p.Val78Ala

c.233T>C · rs1464282313 · VCV1470282

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000427%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6856	likely pathogenic
REVEL	0.452	indeterminate
SaProt	LLR -10.08	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 5.8	GERP 0.53, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 3,545 bp · p 9.1e-15 · regional, not allelic
Overall
CADD	24.0	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 0.000427% European (non-Finnish) · 5/1,169,764 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000316% 5/1,581,366 alleles · very 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.Val78Ala
Coding: c.233T>C
MANE Select: NM_001928
dbSNP: rs1464282313
Type: single nucleotide variant
Location: chr19:860881 (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 78: 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.Val78Phe Uncertain significance ★ ⚠ 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
CFD p.Ala129Thr 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-val78ala (accessed [today's date]).

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