Is DIP2C p.Pro1214= (c.3642C>T) pathogenic?

DIP2C p.Pro1214= (c.3642C>T) is classified Likely benign in DIP2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). Ultra-rare (popmax 0.0176%, sas); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Pro1214= (c.3642C>T)?

DIP2C p.Pro1214= (c.3642C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Pro1214= (c.3642C>T) in the general population?

DIP2C p.Pro1214= (c.3642C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

DIP2C p.Pro1214=

c.3642C>T · rs749942687 · VCV2919705

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.7
Overall
CADD	12.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,078 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00105% 17/1,614,178 alleles · ultra-rare exomes 17/1,461,880 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
European (non-Finnish)	8.47e-05%	1,180,032

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.Pro1214=
Coding: c.3642C>T
MANE Select: NM_014974
dbSNP: rs749942687
Type: single nucleotide variant
Location: chr10:329544 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64

Full DIP2C 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

DIP2C p.Pro1214Ala Uncertain significance ★ ⚠ same residue
DIP2C p.Ala1066Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1101Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1155Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1466Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala193Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala422Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala71Thr 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/dip2c-p-pro1214 (accessed [today's date]).

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