Is DCPS p.Arg264Gln (c.791G>A) pathogenic?

DCPS p.Arg264Gln (c.791G>A) is classified Conflicting classifications of pathogenicity in DCPS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.4679); Rare (popmax 0.395%, sas).

How common is DCPS p.Arg264Gln (c.791G>A) in the general population?

DCPS p.Arg264Gln (c.791G>A) is rare (popmax 0.395%, sas) (gnomAD).

What do computational predictors say about DCPS p.Arg264Gln (c.791G>A)?

AlphaMissense predicts ambiguous (score 0.4679) — an in-silico prediction, not a clinical call.

DCPS p.Arg264Gln

c.791G>A · rs140377449 · VCV377334

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4679 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.395%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4679	ambiguous
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -11.84	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 12	GERP 6.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	25.2	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 0.395% South Asian · 360/91,088 alleles

Filtering AF 0.362% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.348%

Overall 0.074% 1,195/1,614,164 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.395%	253
Middle Eastern	0.297%	337
Admixed American	0.105%	953
Remaining individualsnot grpmax-eligible	0.0736%	1,359
European (non-Finnish)	0.0597%	1,676
African / African-American	0.00533%	18,764

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.Arg264Gln
Coding: c.791G>A
MANE Select: NM_014026
dbSNP: rs140377449
Type: single nucleotide variant
Location: chr11:126345390 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 264: a β-strand

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

Similar variants

DCPS p.Arg264Leu Uncertain significance ★ ⚠ same residue
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

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-arg264gln (accessed [today's date]).

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