Is DCPS p.Thr129Met (c.386C>T) pathogenic?

DCPS p.Thr129Met (c.386C>T) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-19). AlphaMissense: likely benign (0.1474); Ultra-rare (popmax 0.0617%, amr); Associated with Al-Raqad syndrome.

What condition is associated with DCPS p.Thr129Met (c.386C>T)?

DCPS p.Thr129Met (c.386C>T) is associated with Al-Raqad syndrome (ClinVar).

How common is DCPS p.Thr129Met (c.386C>T) in the general population?

DCPS p.Thr129Met (c.386C>T) is ultra-rare (popmax 0.0617%, amr) (gnomAD).

What do computational predictors say about DCPS p.Thr129Met (c.386C>T)?

AlphaMissense predicts likely benign (score 0.1474) — an in-silico prediction, not a clinical call.

DCPS p.Thr129Met

c.386C>T · rs201550193 · VCV1031230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1474 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Al-Raqad syndrome

Computational evidence

Protein change
AlphaMissense	0.1474	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Pangolin	Δ0.24	gain · loss 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 7.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	26.4	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 0.0617% Admixed American · 37/60,014 alleles

Filtering AF 0.0459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0405%

Overall 0.00471% 76/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0617%	1,622
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0048%	20,834
European (non-Finnish)	0.00271%	36,874
East Asian	0.00223%	44,884

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.Thr129Met
Coding: c.386C>T
MANE Select: NM_014026
dbSNP: rs201550193
Type: single nucleotide variant
Location: chr11:126331414 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 129: a β-strand

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.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
DCPS p.Glu286Ter Likely pathogenic ★ same condition
DCPS c.201+4C>G Uncertain significance ★ 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-thr129met (accessed [today's date]).

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