Is DCT p.Pro504Leu (c.1511C>T) pathogenic?

DCT p.Pro504Leu (c.1511C>T) is classified Uncertain significance in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1628); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with DCT p.Pro504Leu (c.1511C>T)?

DCT p.Pro504Leu (c.1511C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCT p.Pro504Leu (c.1511C>T) in the general population?

DCT p.Pro504Leu (c.1511C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about DCT p.Pro504Leu (c.1511C>T)?

AlphaMissense predicts likely benign (score 0.1628) — an in-silico prediction, not a clinical call.

DCT p.Pro504Leu

c.1511C>T · VCV4238257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1628	likely benign
REVEL	0.764	pathogenic-leaning
SaProt	LLR -8.12	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	28.5	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 0.00667% Admixed American · 4/59,978 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,613,736 alleles · very rare

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.Pro504Leu
Coding: c.1511C>T
MANE Select: NM_001922
Type: single nucleotide variant
Location: chr13:94439947 (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-pro504leu (accessed [today's date]).

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