Is CDT1 p.Pro214Ser (c.640C>T) pathogenic?

CDT1 p.Pro214Ser (c.640C>T) is classified Uncertain significance in CDT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.2086); Very rare (popmax 0.00933%, afr).

How common is CDT1 p.Pro214Ser (c.640C>T) in the general population?

CDT1 p.Pro214Ser (c.640C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

What do computational predictors say about CDT1 p.Pro214Ser (c.640C>T)?

AlphaMissense predicts likely benign (score 0.2086) — an in-silico prediction, not a clinical call.

CDT1 p.Pro214Ser

c.640C>T · rs370127987 · VCV1056368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2086	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -3.67	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 7.4	GERP 0.19, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 4,443 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	16.76	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 0.00933% African / African-American · 7/75,056 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000806% 13/1,612,844 alleles · very rare exomes 8/1,460,500 · genomes 5/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,722
Admixed American	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Pro214Ser
Coding: c.640C>T
MANE Select: NM_030928
dbSNP: rs370127987
Type: single nucleotide variant
Location: chr16:88805591 (GRCh38)
Gene constraint: LOEUF 1.737 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.51 · 6 PDB

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-pro214ser (accessed [today's date]).

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