Is DCPS p.Pro235Leu (c.704C>T) pathogenic?

DCPS p.Pro235Leu (c.704C>T) is classified Uncertain significance in DCPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-08). AlphaMissense: likely benign (0.1053); Ultra-rare (popmax 0.0233%, amr); Associated with Inborn genetic diseases.

What condition is associated with DCPS p.Pro235Leu (c.704C>T)?

DCPS p.Pro235Leu (c.704C>T) is associated with Inborn genetic diseases, Al-Raqad syndrome (ClinVar).

How common is DCPS p.Pro235Leu (c.704C>T) in the general population?

DCPS p.Pro235Leu (c.704C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about DCPS p.Pro235Leu (c.704C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

DCPS p.Pro235Leu

c.704C>T · rs151074136 · VCV1033250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -7.75	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 1.8	GERP 5.3, phastCons 0.003
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	19.98	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 0.0233% Admixed American · 14/60,000 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00211% 34/1,613,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
African / African-American	0.00801%	12,487
Remaining individualsnot grpmax-eligible	0.0032%	31,242
South Asian	0.0011%	91,056
European (non-Finnish)	0.000932%	107,270

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.Pro235Leu
Coding: c.704C>T
MANE Select: NM_014026
dbSNP: rs151074136
Type: single nucleotide variant
Location: chr11:126343374 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 235: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Al-Raqad syndrome

Similar variants

DCPS p.Arg152Ter Likely pathogenic ★★ same condition
DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same condition
DCPS p.Arg145Cys 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-pro235leu (accessed [today's date]).

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