Is DCT p.Arg514Gly (c.1540A>G) pathogenic?

DCT p.Arg514Gly (c.1540A>G) is classified Uncertain significance in DCT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0803); Ultra-rare (popmax 0.0446%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCT p.Arg514Gly (c.1540A>G)?

DCT p.Arg514Gly (c.1540A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCT p.Arg514Gly (c.1540A>G) in the general population?

DCT p.Arg514Gly (c.1540A>G) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about DCT p.Arg514Gly (c.1540A>G)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

DCT p.Arg514Gly

c.1540A>G · rs376877447 · VCV3080633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -5.43	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 5.1	GERP 1.9, phastCons 0.95
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	20.4	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 0.0446% East Asian · 20/44,892 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.0013% 21/1,613,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,245
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Arg514Gly
Coding: c.1540A>G
MANE Select: NM_001922
dbSNP: rs376877447
Type: single nucleotide variant
Location: chr13:94439918 (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-arg514gly (accessed [today's date]).

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