Is DCPS p.Asp181Gly (c.542A>G) pathogenic?

DCPS p.Asp181Gly (c.542A>G) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-04). AlphaMissense: likely benign (0.2895); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with DCPS p.Asp181Gly (c.542A>G)?

DCPS p.Asp181Gly (c.542A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCPS p.Asp181Gly (c.542A>G) in the general population?

DCPS p.Asp181Gly (c.542A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DCPS p.Asp181Gly (c.542A>G)?

AlphaMissense predicts likely benign (score 0.2895) — an in-silico prediction, not a clinical call.

DCPS p.Asp181Gly

c.542A>G · VCV3838603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2895 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2895	likely benign
REVEL	0.687	pathogenic-leaning
SaProt	LLR -12.01	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 7.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	28.7	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 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.0013% 21/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed Americangrpmax	0.00333%	30,001
European (non-Finnish)	0.00127%	78,669

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp181Gly
Coding: c.542A>G
MANE Select: NM_014026
Type: single nucleotide variant
Location: chr11:126338305 (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.Asp181His Uncertain significance ★ ⚠ same residue
DCPS p.Asp181Asn Uncertain significance ★ ⚠ same residue
DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same condition
DCPS p.Arg145Cys 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

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-asp181gly (accessed [today's date]).

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