Is CDT1 p.Glu544Val (c.1631A>T) pathogenic?

CDT1 p.Glu544Val (c.1631A>T) is classified Conflicting classifications of pathogenicity in CDT1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1396); Rare (popmax 0.369%, nfe).

How common is CDT1 p.Glu544Val (c.1631A>T) in the general population?

CDT1 p.Glu544Val (c.1631A>T) is rare (popmax 0.369%, nfe) (gnomAD).

What do computational predictors say about CDT1 p.Glu544Val (c.1631A>T)?

AlphaMissense predicts likely benign (score 0.1396) — an in-silico prediction, not a clinical call.

CDT1 p.Glu544Val

c.1631A>T · rs144843732 · VCV128662

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1396 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.369%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1396	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.82	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 0.61, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	15.72	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.369% European (non-Finnish) · 4,316/1,168,218 alleles

Filtering AF 0.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.356%

Overall 0.287% 4,555/1,589,160 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.369%	271
Remaining individualsnot grpmax-eligible	0.221%	453
Admixed American	0.0731%	1,368
Finnishnot grpmax-eligible	0.056%	1,787
African / African-American	0.0308%	3,245
Ashkenazi Jewishnot grpmax-eligible	0.0138%	7,259
South Asian	0.00113%	88,114

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: CDT1
Protein: p.Glu544Val
Coding: c.1631A>T
MANE Select: NM_030928
dbSNP: rs144843732
Type: single nucleotide variant
Location: chr16:88808268 (GRCh38)
Gene constraint: LOEUF 1.737 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.51 · 6 PDB
Residue 544: the 'interaction with lrwd1' region

Full CDT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDT1 p.Glu544Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
CDT1 c.832+1G>A Pathogenic/Likely pathogenic ★★ same type
CDT1 p.Arg462Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
CDT1 p.Ala11Val Uncertain significance ★★ ⚠ same type
CDT1 p.Ala144Ser Uncertain significance ★★ ⚠ same type
CDT1 p.Ala167Thr Uncertain significance ★★ ⚠ same type
CDT1 p.Ala217Val Uncertain significance ★★ ⚠ same type
CDT1 p.Ala414Ser 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/cdt1-p-glu544val (accessed [today's date]).

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