Is CDT1 p.Ala135Val (c.404C>T) pathogenic?

CDT1 p.Ala135Val (c.404C>T) is classified Benign/Likely benign in CDT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0943); Low-frequency (popmax 1.31%, afr).

How common is CDT1 p.Ala135Val (c.404C>T) in the general population?

CDT1 p.Ala135Val (c.404C>T) is low-frequency (popmax 1.31%, afr) (gnomAD).

What do computational predictors say about CDT1 p.Ala135Val (c.404C>T)?

AlphaMissense predicts likely benign (score 0.0943) — an in-silico prediction, not a clinical call.

CDT1 p.Ala135Val

c.404C>T · rs3218725 · VCV128676

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0943 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0943	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -9.25	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 0.94	GERP -2.6, phastCons 0.002
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	18.75	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 1.31% African / African-American · 982/75,042 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.21%

Overall 0.0879% 1,417/1,612,612 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.31%	76
Admixed American	0.225%	445
Remaining individualsnot grpmax-eligible	0.167%	600
Middle Eastern	0.115%	866
European (non-Finnish)	0.0158%	6,343
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
South Asian	0.0022%	45,542

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.Ala135Val
Coding: c.404C>T
MANE Select: NM_030928
dbSNP: rs3218725
Type: single nucleotide variant
Location: chr16:88804814 (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 135: a UniProt-annotated variant site (in)

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

Similar variants

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
CDT1 p.Ala431Thr 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-ala135val (accessed [today's date]).

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