Is DIP2C p.Gly8Asp (c.23G>A) pathogenic?

DIP2C p.Gly8Asp (c.23G>A) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely benign (0.1336); Very rare (popmax 0.000101%, nfe).

How common is DIP2C p.Gly8Asp (c.23G>A) in the general population?

DIP2C p.Gly8Asp (c.23G>A) is very rare (popmax 0.000101%, nfe) (gnomAD).

What do computational predictors say about DIP2C p.Gly8Asp (c.23G>A)?

AlphaMissense predicts likely benign (score 0.1336) — an in-silico prediction, not a clinical call.

DIP2C p.Gly8Asp

c.23G>A · rs761909966 · VCV1949201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000101%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1336	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.00	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 6.4	GERP -2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.000101% European (non-Finnish) · 1/989,564 alleles

Overall 8.95e-05% 1/1,117,656 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.Gly8Asp
Coding: c.23G>A
MANE Select: NM_014974
dbSNP: rs761909966
Type: single nucleotide variant
Location: chr10:689556 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 8: 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-gly8asp (accessed [today's date]).

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