Is CDRT4 p.Arg20Trp (c.58C>T) pathogenic?

CDRT4 p.Arg20Trp (c.58C>T) is classified Uncertain significance in CDRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.0165%, sas).

How common is CDRT4 p.Arg20Trp (c.58C>T) in the general population?

CDRT4 p.Arg20Trp (c.58C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

What do computational predictors say about CDRT4 p.Arg20Trp (c.58C>T)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

CDRT4 p.Arg20Trp

c.58C>T · rs781118198 · VCV2510869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -5.55	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 0.16	GERP -4.1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,462 bp · p 0.061 · regional, not allelic
Overall
CADD	16.38	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 0.0165% South Asian · 15/91,072 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00415% 67/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
Admixed American	0.00834%	11,997
East Asian	0.00445%	22,450
European (non-Finnish)	0.00356%	28,092
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00134%	74,858

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.Arg20Trp
Coding: c.58C>T
MANE Select: NM_001204477
dbSNP: rs781118198
Type: single nucleotide variant
Location: chr17:15438174 (GRCh38)
Gene constraint: LOEUF 1.287 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 66.42
Residue 20: the 'disordered' region

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

Similar variants

CDRT4 p.Arg20Gln Uncertain significance ★ ⚠ same residue
CDRT4 p.Arg140His Uncertain significance ★ ⚠ same type
CDRT4 p.Arg140Leu Uncertain significance ★ ⚠ same type
CDRT4 p.Arg151Cys 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-arg20trp (accessed [today's date]).

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