Is DCPS p.Arg257Trp (c.769C>T) pathogenic?

DCPS p.Arg257Trp (c.769C>T) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-11). AlphaMissense: likely benign (0.1555); Rare (popmax 0.245%, afr).

How common is DCPS p.Arg257Trp (c.769C>T) in the general population?

DCPS p.Arg257Trp (c.769C>T) is rare (popmax 0.245%, afr) (gnomAD).

What do computational predictors say about DCPS p.Arg257Trp (c.769C>T)?

AlphaMissense predicts likely benign (score 0.1555) — an in-silico prediction, not a clinical call.

DCPS p.Arg257Trp

c.769C>T · rs146794173 · VCV501414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1555 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.245%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1555	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 5.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	26.1	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 0.245% African / African-American · 184/75,046 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0186% 300/1,614,034 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.245%	408
Finnishnot grpmax-eligible	0.108%	926
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.015%	6,670
South Asian	0.00329%	30,362
European (non-Finnish)	0.00186%	53,637

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.Arg257Trp
Coding: c.769C>T
MANE Select: NM_014026
dbSNP: rs146794173
Type: single nucleotide variant
Location: chr11:126345368 (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

Similar variants

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
DCPS p.Asp324= 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-arg257trp (accessed [today's date]).

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