Is DCTPP1 p.Pro115Ala (c.343C>G) pathogenic?

DCTPP1 p.Pro115Ala (c.343C>G) is classified Uncertain significance in DCTPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.3111); Very rare (popmax 0.00288%, nfe).

How common is DCTPP1 p.Pro115Ala (c.343C>G) in the general population?

DCTPP1 p.Pro115Ala (c.343C>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about DCTPP1 p.Pro115Ala (c.343C>G)?

AlphaMissense predicts likely benign (score 0.3111) — an in-silico prediction, not a clinical call.

DCTPP1 p.Pro115Ala

c.343C>G · VCV4829164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3111	likely benign
REVEL	0.488	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,744 bp · p 0.97 · regional, not allelic
Overall
CADD	24.4	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 0.00288% European (non-Finnish) · 34/1,179,984 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00211% 34/1,613,900 alleles · very rare

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: DCTPP1
Protein: p.Pro115Ala
Coding: c.343C>G
MANE Select: NM_024096
Type: single nucleotide variant
Location: chr16:30424403 (GRCh38)
Gene constraint: LOEUF 1.458 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 5 PDB
Residue 115: an α-helix

Full DCTPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCTPP1 p.Pro115Arg Uncertain significance ★ ⚠ same residue
DCTPP1 p.Pro115Leu Uncertain significance ★ ⚠ same residue
DCTPP1 p.Ala18Pro Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg109Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg111Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg126Trp Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg135Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg135His Uncertain significance ★ ⚠ 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/dctpp1-p-pro115ala (accessed [today's date]).

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