Is DIP2C p.Asp84His (c.250G>C) pathogenic?

DIP2C p.Asp84His (c.250G>C) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely pathogenic (0.9869); Absent from gnomAD v4.1.

How common is DIP2C p.Asp84His (c.250G>C) in the general population?

DIP2C p.Asp84His (c.250G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2C p.Asp84His (c.250G>C)?

AlphaMissense predicts likely pathogenic (score 0.9869) — an in-silico prediction, not a clinical call.

DIP2C p.Asp84His

c.250G>C · VCV3907730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9869 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9869	likely pathogenic
REVEL	0.396	indeterminate
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DIP2C
Protein: p.Asp84His
Coding: c.250G>C
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:472457 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 84: the dmap1-binding domain; the 'disordered' region

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-asp84his (accessed [today's date]).

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