Is DIP2C p.Thr67Ile (c.200C>T) pathogenic?

DIP2C p.Thr67Ile (c.200C>T) is classified Conflicting classifications of pathogenicity in DIP2C (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1386); Ultra-rare (popmax 0.0416%, amr); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Thr67Ile (c.200C>T)?

DIP2C p.Thr67Ile (c.200C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Thr67Ile (c.200C>T) in the general population?

DIP2C p.Thr67Ile (c.200C>T) is ultra-rare (popmax 0.0416%, amr) (gnomAD).

What do computational predictors say about DIP2C p.Thr67Ile (c.200C>T)?

AlphaMissense predicts likely benign (score 0.1386) — an in-silico prediction, not a clinical call.

DIP2C p.Thr67Ile

c.200C>T · rs752352624 · VCV1416620

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1386 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1386	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -7.58	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 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	22.4	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 0.0416% Admixed American · 25/60,030 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00185% 27/1,461,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0416%	2,401
Middle Eastern	0.0165%	6,062
European (non-Finnish)	8.47e-05%	1,180,043

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.Thr67Ile
Coding: c.200C>T
MANE Select: NM_014974
dbSNP: rs752352624
Type: single nucleotide variant
Location: chr10:472507 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 67: the dmap1-binding domain; the 'disordered' region

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.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
DIP2C p.Ala997Val 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-thr67ile (accessed [today's date]).

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