Is DCPS p.Ser45Cys (c.134C>G) pathogenic?

DCPS p.Ser45Cys (c.134C>G) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.091); Very rare (popmax 0.01%, amr).

How common is DCPS p.Ser45Cys (c.134C>G) in the general population?

DCPS p.Ser45Cys (c.134C>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DCPS p.Ser45Cys (c.134C>G)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

DCPS p.Ser45Cys

c.134C>G · VCV3343505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -5.55	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 6	GERP 2.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	25.7	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 0.01% Admixed American · 6/60,028 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00248% 40/1,614,238 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,005
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.00271%	36,876

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.Ser45Cys
Coding: c.134C>G
MANE Select: NM_014026
Type: single nucleotide variant
Location: chr11:126304214 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 45: a β-strand

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-ser45cys (accessed [today's date]).

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