Is DCPS p.Asp181His (c.541G>C) pathogenic?

DCPS p.Asp181His (c.541G>C) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: ambiguous (0.4746); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCPS p.Asp181His (c.541G>C)?

DCPS p.Asp181His (c.541G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCPS p.Asp181His (c.541G>C) in the general population?

DCPS p.Asp181His (c.541G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCPS p.Asp181His (c.541G>C)?

AlphaMissense predicts ambiguous (score 0.4746) — an in-silico prediction, not a clinical call.

DCPS p.Asp181His

c.541G>C · rs772776014 · VCV2339155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4746 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4746	ambiguous
REVEL	0.673	pathogenic-leaning
SaProt	LLR -13.87	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 6.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	28.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCPS
Protein: p.Asp181His
Coding: c.541G>C
MANE Select: NM_014026
dbSNP: rs772776014
Type: single nucleotide variant
Location: chr11:126338304 (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.Asp181Gly 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-asp181his (accessed [today's date]).

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