Is CDPF1 p.Arg91Trp (c.271C>T) pathogenic?

CDPF1 p.Arg91Trp (c.271C>T) is classified Uncertain significance in CDPF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.079); Ultra-rare (popmax 0.0178%, eas).

How common is CDPF1 p.Arg91Trp (c.271C>T) in the general population?

CDPF1 p.Arg91Trp (c.271C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CDPF1 p.Arg91Trp (c.271C>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

CDPF1 p.Arg91Trp

c.271C>T · VCV3999824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -9.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP -0.32, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 3,189 bp · p 0.73 · regional, not allelic
Overall
CADD	21.2	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 0.0178% East Asian · 8/44,904 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00273% 44/1,614,056 alleles · ultra-rare exomes 34/1,461,844 · genomes 10/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,613
Admixed American	0.0133%	7,500
South Asian	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00161%	62,106

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.Arg91Trp
Coding: c.271C>T
MANE Select: NM_207327
Type: single nucleotide variant
Location: chr22:46245193 (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

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CDPF1 p.Cys64Arg Uncertain significance ★ ⚠ same type
CDPF1 p.Cys86Phe Uncertain significance ★ ⚠ same type
CDPF1 p.Glu41Lys Uncertain significance ★ ⚠ same type
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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-arg91trp (accessed [today's date]).

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