Is DCPS p.Asp181Asn (c.541G>A) pathogenic?

DCPS p.Asp181Asn (c.541G>A) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-19). AlphaMissense: likely benign (0.1739); Very rare (popmax 0.00729%, nfe); Associated with Al-Raqad syndrome.

What condition is associated with DCPS p.Asp181Asn (c.541G>A)?

DCPS p.Asp181Asn (c.541G>A) is associated with Al-Raqad syndrome (ClinVar).

How common is DCPS p.Asp181Asn (c.541G>A) in the general population?

DCPS p.Asp181Asn (c.541G>A) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about DCPS p.Asp181Asn (c.541G>A)?

AlphaMissense predicts likely benign (score 0.1739) — an in-silico prediction, not a clinical call.

DCPS p.Asp181Asn

c.541G>A · rs772776014 · VCV1033249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Al-Raqad syndrome

Computational evidence

Protein change
AlphaMissense	0.1739	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
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	29.8	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 0.00729% European (non-Finnish) · 86/1,180,038 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00576% 93/1,614,008 alleles · very rare exomes 87/1,461,884 · genomes 6/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,721
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.00333%	29,997
African / African-American	0.00134%	74,902

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.Asp181Asn
Coding: c.541G>A
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

Al-Raqad syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCPS p.Asp181Gly Uncertain significance ★ ⚠ same residue
DCPS p.Asp181His Uncertain significance ★ ⚠ same residue
DCPS p.Arg152Ter Likely pathogenic ★★ same condition
DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same condition
DCPS p.Pro235Leu Uncertain significance ★★ ⚠ same condition
DCPS p.Gln105= Benign ★★ same condition
DCPS p.Phe63= Benign ★★ same condition
DCPS c.201+1G>T Likely pathogenic ★ 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-asp181asn (accessed [today's date]).

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