Is DIP2C p.Pro12Ser (c.34C>T) pathogenic?

DIP2C p.Pro12Ser (c.34C>T) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-01). AlphaMissense: likely pathogenic (0.6811); Very rare (popmax 8.77e-05%).

How common is DIP2C p.Pro12Ser (c.34C>T) in the general population?

DIP2C p.Pro12Ser (c.34C>T) is very rare (popmax 8.77e-05%) (gnomAD).

What do computational predictors say about DIP2C p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely pathogenic (score 0.6811) — an in-silico prediction, not a clinical call.

DIP2C p.Pro12Ser

c.34C>T · VCV4823741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.77e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6811	likely pathogenic
REVEL	0.677	pathogenic-leaning
SaProt	LLR -10.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.77e-05%

Overall 8.77e-05% 1/1,140,220 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: DIP2C
Protein: p.Pro12Ser
Coding: c.34C>T
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:689545 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 12: the dmap1-binding domain

Full DIP2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIP2C p.Ala1066Thr Uncertain significance ★★ ⚠ same type
DIP2C p.Ala1066Val Uncertain significance ★★ ⚠ same type
DIP2C p.Ala1101Val Uncertain significance ★★ ⚠ same type
DIP2C p.Ala1155Thr Uncertain significance ★★ ⚠ same type
DIP2C p.Ala1466Thr Uncertain significance ★★ ⚠ same type
DIP2C p.Ala193Val Uncertain significance ★★ ⚠ same type
DIP2C p.Ala422Thr Uncertain significance ★★ ⚠ same type
DIP2C p.Ala71Thr 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/dip2c-p-pro12ser (accessed [today's date]).

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