Is DCPS p.Arg145Cys (c.433C>T) pathogenic?

DCPS p.Arg145Cys (c.433C>T) is classified Uncertain significance in DCPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0428%, sas); Associated with Inborn genetic diseases.

What condition is associated with DCPS p.Arg145Cys (c.433C>T)?

DCPS p.Arg145Cys (c.433C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCPS p.Arg145Cys (c.433C>T) in the general population?

DCPS p.Arg145Cys (c.433C>T) is ultra-rare (popmax 0.0428%, sas) (gnomAD).

What do computational predictors say about DCPS p.Arg145Cys (c.433C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

DCPS p.Arg145Cys

c.433C>T · rs201132569 · VCV424491

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0428%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 6.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	26.2	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 0.0428% South Asian · 39/91,080 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0284%

Overall 0.00384% 62/1,614,152 alleles · ultra-rare exomes 59/1,461,882 · genomes 3/152,270 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0428%	2,335
East Asian	0.0223%	4,487
Remaining individualsnot grpmax-eligible	0.0064%	15,626
African / African-American	0.00267%	37,522
European (non-Finnish)	0.000593%	168,575

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.Arg145Cys
Coding: c.433C>T
MANE Select: NM_014026
dbSNP: rs201132569
Type: single nucleotide variant
Location: chr11:126331461 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB

Full DCPS 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

DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same condition
DCPS p.Pro235Leu Uncertain significance ★★ ⚠ same condition
DCPS p.Ala186Val Uncertain significance ★ ⚠ same condition
DCPS p.Ala251Val Uncertain significance ★ ⚠ same condition
DCPS p.Ala282Thr Uncertain significance ★ ⚠ same condition
DCPS p.Ala287Thr Uncertain significance ★ ⚠ same condition
DCPS p.Ala287Val Uncertain significance ★ same condition
DCPS p.Ala295Val 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/dcps-p-arg145cys (accessed [today's date]).

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