Is DCPS p.Ser290Ala (c.868T>G) pathogenic?

DCPS p.Ser290Ala (c.868T>G) is classified Likely benign in DCPS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0738); Rare (popmax 0.313%, mid).

How common is DCPS p.Ser290Ala (c.868T>G) in the general population?

DCPS p.Ser290Ala (c.868T>G) is rare (popmax 0.313%, mid) (gnomAD).

What do computational predictors say about DCPS p.Ser290Ala (c.868T>G)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

DCPS p.Ser290Ala

c.868T>G · rs143135288 · VCV782778

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.313%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP 0.34
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	10.17	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 0.313% Middle Eastern · 19/6,062 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.157% 2,530/1,614,142 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.473%	211
Middle Easterngrpmax	0.313%	319
South Asian	0.18%	555
European (non-Finnish)	0.167%	599
Remaining individualsnot grpmax-eligible	0.16%	625
Finnishnot grpmax-eligible	0.123%	810
Admixed American	0.06%	1,667
African / African-American	0.0293%	3,411
East Asian	0.00223%	44,892

Ashkenazi Jewish 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.Ser290Ala
Coding: c.868T>G
MANE Select: NM_014026
dbSNP: rs143135288
Type: single nucleotide variant
Location: chr11:126345467 (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-ser290ala (accessed [today's date]).

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