Is DCT p.Arg275Gln (c.824G>A) pathogenic?

DCT p.Arg275Gln (c.824G>A) is classified Benign in DCT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-09). AlphaMissense: likely benign (0.0581); Low-frequency (popmax 3.78%, afr).

How common is DCT p.Arg275Gln (c.824G>A) in the general population?

DCT p.Arg275Gln (c.824G>A) is low-frequency (popmax 3.78%, afr) (gnomAD).

What do computational predictors say about DCT p.Arg275Gln (c.824G>A)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

DCT p.Arg275Gln

c.824G>A · rs34139115 · VCV709290

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.78%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.32	donor loss, 39 bp away · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.59	GERP -5.4, phastCons 0.002
Regional constraint	o/e 1.05	unconstrained · MANE · 39 kb · p 0.21 · regional, not allelic
Overall
CADD	8.989	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 3.78% African / African-American · 2,827/74,884 alleles

Filtering AF 3.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.61%

Overall 0.2% 3,223/1,613,386 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.78%	26
Remaining individualsnot grpmax-eligible	0.27%	370
Admixed American	0.252%	397
Middle Eastern	0.165%	606
South Asian	0.00879%	11,379
European (non-Finnish)	0.00483%	20,698
Finnishnot grpmax-eligible	0.00156%	63,950

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.Arg275Gln
Coding: c.824G>A
MANE Select: NM_001922
dbSNP: rs34139115
Type: single nucleotide variant
Location: chr13:94465672 (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

Similar variants

DCT p.Arg275Trp Uncertain significance ★ ⚠ same residue
DCT p.Arg233Ter Pathogenic/Likely pathogenic ★★ same type
DCT p.Thr114= Benign ★★ same type
DCT p.Arg326Ter Pathogenic ★ same type
DCT p.Trp71Ter Pathogenic ★ same type
DCT c.1180-2098C>T Uncertain significance ★ same type
DCT c.1180-2111A>G Uncertain significance ★ same type
DCT p.Ala144Thr 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/dct-p-arg275gln (accessed [today's date]).

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