Is CDPF1 p.Arg8Cys (c.22C>T) pathogenic?

CDPF1 p.Arg8Cys (c.22C>T) is classified Uncertain significance in CDPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0754); Very rare (popmax 0.008%, afr).

How common is CDPF1 p.Arg8Cys (c.22C>T) in the general population?

CDPF1 p.Arg8Cys (c.22C>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about CDPF1 p.Arg8Cys (c.22C>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

CDPF1 p.Arg8Cys

c.22C>T · rs547032323 · VCV3141690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.96	GERP -3.1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,189 bp · p 0.73 · regional, not allelic
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.008% African / African-American · 6/75,000 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.0031% 50/1,613,160 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,500
European (non-Finnish)	0.00348%	28,768
Remaining individualsnot grpmax-eligible	0.0032%	31,235
Admixed American	0.00167%	59,968

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: CDPF1
Protein: p.Arg8Cys
Coding: c.22C>T
MANE Select: NM_207327
dbSNP: rs547032323
Type: single nucleotide variant
Location: chr22:46248263 (GRCh38)
Gene constraint: LOEUF 1.566 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30

Full CDPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDPF1 p.Arg8His Uncertain significance ★ ⚠ same residue
CDPF1 p.Arg102Trp Uncertain significance ★ ⚠ same type
CDPF1 p.Arg91Trp Uncertain significance ★ ⚠ same type
CDPF1 p.Cys64Arg Uncertain significance ★ ⚠ same type
CDPF1 p.Cys86Phe Uncertain significance ★ ⚠ same type
CDPF1 p.Glu41Lys Uncertain significance ★ ⚠ same type
CDPF1 p.Glu92Lys Uncertain significance ★ ⚠ same type
CDPF1 p.Gly28Ala 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/cdpf1-p-arg8cys (accessed [today's date]).

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