Is DCPS p.Pro239Leu (c.716C>T) pathogenic?

DCPS p.Pro239Leu (c.716C>T) is classified Uncertain significance in DCPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2393); Ultra-rare (popmax 0.0231%, sas); Associated with Inborn genetic diseases.

What condition is associated with DCPS p.Pro239Leu (c.716C>T)?

DCPS p.Pro239Leu (c.716C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCPS p.Pro239Leu (c.716C>T) in the general population?

DCPS p.Pro239Leu (c.716C>T) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about DCPS p.Pro239Leu (c.716C>T)?

AlphaMissense predicts likely benign (score 0.2393) — an in-silico prediction, not a clinical call.

DCPS p.Pro239Leu

c.716C>T · VCV4617008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2393 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2393	likely benign
REVEL	0.753	pathogenic-leaning
SaProt	LLR -10.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 6.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 42 kb · p 0.2 · regional, not allelic
Overall
CADD	28.3	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 0.0231% South Asian · 21/91,024 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00254% 41/1,613,726 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,334
Admixed American	0.00667%	14,995
East Asian	0.00446%	22,441
African / African-American	0.004%	24,971
European (non-Finnish)	0.000932%	107,264

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.Pro239Leu
Coding: c.716C>T
MANE Select: NM_014026
Type: single nucleotide variant
Location: chr11:126343386 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.18 · 11 PDB
Residue 239: 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

Similar variants

DCPS p.Pro239Ser Uncertain significance ★ ⚠ same residue
DCPS p.Pro239= Benign ★ same residue
DCPS p.Ala184Thr Uncertain significance ★★ ⚠ same condition
DCPS p.Arg145Cys Uncertain significance ★★ ⚠ same condition
DCPS p.Pro235Leu Uncertain significance ★★ ⚠ same condition
DCPS p.Ala186Val Uncertain significance ★ ⚠ same condition
DCPS p.Ala251Val Uncertain significance ★ ⚠ same condition
DCPS p.Ala282Thr 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-pro239leu (accessed [today's date]).

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