Is DCT p.Pro270Leu (c.809C>T) pathogenic?

DCT p.Pro270Leu (c.809C>T) is classified Uncertain significance in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.0982); Rare (popmax 0.17%, sas); Associated with Inborn genetic diseases.

What condition is associated with DCT p.Pro270Leu (c.809C>T)?

DCT p.Pro270Leu (c.809C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCT p.Pro270Leu (c.809C>T) in the general population?

DCT p.Pro270Leu (c.809C>T) is rare (popmax 0.17%, sas) (gnomAD).

What do computational predictors say about DCT p.Pro270Leu (c.809C>T)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

DCT p.Pro270Leu

c.809C>T · VCV3838642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.17%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -9.32	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 10	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	22.1	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 0.17% South Asian · 155/91,038 alleles

Filtering AF 0.148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.0136% 219/1,613,428 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.17%	587
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Finnishnot grpmax-eligible	0.00782%	12,790
European (non-Finnish)	0.00398%	25,103
African / African-American	0.00267%	37,433
Admixed American	0.00167%	59,936

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: DCT
Protein: p.Pro270Leu
Coding: c.809C>T
MANE Select: NM_001922
Type: single nucleotide variant
Location: chr13:94465687 (GRCh38)
Gene constraint: LOEUF 1.101 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.33 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCT c.1180-2098C>T Uncertain significance ★ same condition
DCT c.1180-2111A>G Uncertain significance ★ same condition
DCT p.Ala144Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala206Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala357Glu Uncertain significance ★ ⚠ same condition
DCT p.Ala381Thr Uncertain significance ★ ⚠ same condition
DCT p.Ala386Thr Uncertain significance ★ ⚠ same condition
DCT p.Arg202Cys Uncertain significance ★ ⚠ same condition

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/dct-p-pro270leu (accessed [today's date]).

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