Is CDT1 p.Ala537Val (c.1610C>T) pathogenic?

CDT1 p.Ala537Val (c.1610C>T) is classified Benign in CDT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0882); Common (popmax 6.43%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CDT1 p.Ala537Val (c.1610C>T)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

CDT1 p.Ala537Val

Q: How common is CDT1 p.Ala537Val (c.1610C>T) in the general population?

CDT1 p.Ala537Val (c.1610C>T) is common (popmax 6.43%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1610C>T · rs3218721 · VCV128674

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.43%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -8.16	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 0.86	GERP -0.97, phastCons 0.28
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	13.12	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 6.43% African / African-American · 4,815/74,878 alleles

Filtering AF 6.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.22%

Overall 0.413% 6,615/1,601,962 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.43%	16
South Asian	1.01%	99
Remaining individualsnot grpmax-eligible	0.653%	153
Middle Eastern	0.595%	168
Admixed American	0.587%	170
European (non-Finnish)	0.00979%	10,217
East Asian	0.0045%	22,212

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.Ala537Val
Coding: c.1610C>T
MANE Select: NM_030928
dbSNP: rs3218721
Type: single nucleotide variant
Location: chr16:88808247 (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 537: a UniProt-annotated variant site (in); the 'interaction with lrwd1' region

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

Similar variants

CDT1 p.Ala537Thr Uncertain significance ★ ⚠ 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-ala537val (accessed [today's date]).

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