Is CDRT4 p.Pro30Leu (c.89C>T) pathogenic?

CDRT4 p.Pro30Leu (c.89C>T) is classified Uncertain significance in CDRT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.3015); Ultra-rare (popmax 0.0648%, sas).

How common is CDRT4 p.Pro30Leu (c.89C>T) in the general population?

CDRT4 p.Pro30Leu (c.89C>T) is ultra-rare (popmax 0.0648%, sas) (gnomAD).

What do computational predictors say about CDRT4 p.Pro30Leu (c.89C>T)?

AlphaMissense predicts likely benign (score 0.3015) — an in-silico prediction, not a clinical call.

CDRT4 p.Pro30Leu

c.89C>T · rs149332799 · VCV2370756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3015 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0648%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3015	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,462 bp · p 0.061 · regional, not allelic
Overall
CADD	25.3	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 0.0648% South Asian · 59/91,074 alleles

Filtering AF 0.0515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00545% 88/1,613,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0648%	1,544
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00223%	44,900
European (non-Finnish)	0.00169%	59,002
Admixed American	0.00167%	59,982
Finnishnot grpmax-eligible	0.00156%	63,998
African / African-American	0.00134%	74,892

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.Pro30Leu
Coding: c.89C>T
MANE Select: NM_001204477
dbSNP: rs149332799
Type: single nucleotide variant
Location: chr17:15438143 (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.Arg151Cys 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

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-pro30leu (accessed [today's date]).

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