Is DIP2C p.Ala1274= (c.3822A>G) pathogenic?

DIP2C p.Ala1274= (c.3822A>G) is classified Benign in DIP2C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 18.8%, eas) — too common for a highly-penetrant pathogenic allele.

DIP2C p.Ala1274=

Q: How common is DIP2C p.Ala1274= (c.3822A>G) in the general population?

DIP2C p.Ala1274= (c.3822A>G) is common (popmax 18.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3822A>G · rs2288681 · VCV1673071

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 18.8%, 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	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.1	GERP -5.2
Overall
CADD	0.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.8% East Asian · 8,415/44,858 alleles

Filtering AF 18.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.3%

Overall 6.94% 112,084/1,613,942 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	18.8%	5
African / African-American	17%	6
South Asian	14.6%	7
Middle Eastern	8.81%	11
Remaining individualsnot grpmax-eligible	8.09%	12
Finnishnot grpmax-eligible	5.89%	17
European (non-Finnish)	5.41%	18
Ashkenazi Jewishnot grpmax-eligible	5.41%	18
Amishnot grpmax-eligible	4.71%	21
Admixed American	4.66%	21

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.Ala1274=
Coding: c.3822A>G
MANE Select: NM_014974
dbSNP: rs2288681
Type: single nucleotide variant
Location: chr10:327108 (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.Ala1274Thr 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-ala1274 (accessed [today's date]).

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