Is DIP2C p.Gly622= (c.1866C>T) pathogenic?

DIP2C p.Gly622= (c.1866C>T) is classified Benign in DIP2C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 48.4%, eas) — too common for a highly-penetrant pathogenic allele.

DIP2C p.Gly622=

Q: How common is DIP2C p.Gly622= (c.1866C>T) in the general population?

DIP2C p.Gly622= (c.1866C>T) is common (popmax 48.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1866C>T · rs10904083 · VCV1645858

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 48.4%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.7
Overall
CADD	0.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.4% East Asian · 21,158/43,694 alleles

Filtering AF 47.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.7%

Overall 35.3% 564,158/1,597,882 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	48.4%	2
Admixed American	45.7%	2
South Asian	44.6%	2
Finnishnot grpmax-eligible	42.5%	2
Ashkenazi Jewishnot grpmax-eligible	37.4%	3
Remaining individualsnot grpmax-eligible	35.4%	3
Middle Eastern	34.1%	3
European (non-Finnish)	33.6%	3
African / African-American	29.3%	3
Amishnot grpmax-eligible	24.5%	4

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.Gly622=
Coding: c.1866C>T
MANE Select: NM_014974
dbSNP: rs10904083
Type: single nucleotide variant
Location: chr10:384037 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 622: a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)

Full DIP2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIP2C p.Gly622Ser 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-gly622 (accessed [today's date]).

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