Is DIP2C p.His681Gln (c.2043T>G) pathogenic?

DIP2C p.His681Gln (c.2043T>G) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1048); Absent from gnomAD v4.1.

How common is DIP2C p.His681Gln (c.2043T>G) in the general population?

DIP2C p.His681Gln (c.2043T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2C p.His681Gln (c.2043T>G)?

AlphaMissense predicts likely benign (score 0.1048) — an in-silico prediction, not a clinical call.

DIP2C p.His681Gln

c.2043T>G · rs2132783219 · VCV1480312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1048 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1048	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -1.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.43	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -8.3	GERP -3.7
Regional constraint	o/e 0.68	unconstrained · MANE · 54 kb · p 2.7e-23 · regional, not allelic
Overall
CADD	0.061	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

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.His681Gln
Coding: c.2043T>G
MANE Select: NM_014974
dbSNP: rs2132783219
Type: single nucleotide variant
Location: chr10:369582 (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

Similar variants

DIP2C p.His681Arg Uncertain significance ★ ⚠ same residue
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

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-his681gln (accessed [today's date]).

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