Is DCPS p.Arg188Trp (c.562C>T) pathogenic?

DCPS p.Arg188Trp (c.562C>T) is classified Likely pathogenic in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2015-08-30). AlphaMissense: likely pathogenic (0.6419); Ultra-rare (popmax 0.0233%, amr).

How common is DCPS p.Arg188Trp (c.562C>T) in the general population?

DCPS p.Arg188Trp (c.562C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about DCPS p.Arg188Trp (c.562C>T)?

AlphaMissense predicts likely pathogenic (score 0.6419) — an in-silico prediction, not a clinical call.

DCPS p.Arg188Trp

c.562C>T · rs556401323 · VCV430387

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6419 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6419	likely pathogenic ✓ concordant with ClinVar
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -14.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 6.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	31.0	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 0.0233% Admixed American · 14/60,018 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00595% 96/1,614,140 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,287
South Asian	0.0231%	4,337
African / African-American	0.0227%	4,413
Remaining individualsnot grpmax-eligible	0.008%	12,502
Finnishnot grpmax-eligible	0.00469%	21,340
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00297%	33,715

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: DCPS
Protein: p.Arg188Trp
Coding: c.562C>T
MANE Select: NM_014026
dbSNP: rs556401323
Type: single nucleotide variant
Location: chr11:126338325 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 188: an α-helix

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

Similar variants

DCPS p.Arg152Ter Likely pathogenic ★★ same type
DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same type
DCPS p.Arg145Cys Uncertain significance ★★ ⚠ same type
DCPS p.Arg242Gly Uncertain significance ★★ ⚠ same type
DCPS p.Pro235Leu Uncertain significance ★★ ⚠ same type
DCPS p.Ala186= Benign/Likely benign ★★ same type
DCPS p.Ala80= Likely benign ★★ same type
DCPS p.Asp324= Likely benign ★★ 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/dcps-p-arg188trp (accessed [today's date]).

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