Is CDRT4 p.Arg151Cys (c.451C>T) pathogenic?

CDRT4 p.Arg151Cys (c.451C>T) is classified Uncertain significance in CDRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1357); Very rare (popmax 0.00669%, eas).

How common is CDRT4 p.Arg151Cys (c.451C>T) in the general population?

CDRT4 p.Arg151Cys (c.451C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CDRT4 p.Arg151Cys (c.451C>T)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

CDRT4 p.Arg151Cys

c.451C>T · VCV4651677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.15	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 2.8	GERP -2.2, phastCons 0.24
Regional constraint	o/e 0.87	unconstrained · MANE · 2,462 bp · p 0.061 · regional, not allelic
Overall
CADD	15.38	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 0.00669% East Asian · 3/44,856 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00124% 20/1,613,380 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,952
Admixed American	0.00667%	15,002
South Asian	0.0011%	91,070
European (non-Finnish)	0.00102%	98,289

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: CDRT4
Protein: p.Arg151Cys
Coding: c.451C>T
MANE Select: NM_001204477
Type: single nucleotide variant
Location: chr17:15437781 (GRCh38)
Gene constraint: LOEUF 1.287 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 66.42

Full CDRT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDRT4 p.Arg140His Uncertain significance ★ ⚠ same type
CDRT4 p.Arg140Leu Uncertain significance ★ ⚠ same type
CDRT4 p.Arg20Gln Uncertain significance ★ ⚠ same type
CDRT4 p.Arg20Trp Uncertain significance ★ ⚠ same type
CDRT4 p.Arg78Lys Uncertain significance ★ ⚠ same type
CDRT4 p.Glu60Gly Uncertain significance ★ ⚠ same type
CDRT4 p.Gly103Val Uncertain significance ★ ⚠ same type
CDRT4 p.Met143Thr 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/cdrt4-p-arg151cys (accessed [today's date]).

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