Is DIP2C p.Leu324= (c.970C>T) pathogenic?

DIP2C p.Leu324= (c.970C>T) is classified Benign in DIP2C (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 71.1%, eas) — too common for a highly-penetrant pathogenic allele.

DIP2C p.Leu324=

Q: How common is DIP2C p.Leu324= (c.970C>T) in the general population?

DIP2C p.Leu324= (c.970C>T) is common (popmax 71.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.970C>T · rs4881274 · VCV1242047

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 71.1%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP -2.1, phastCons 0.018
Overall
CADD	4.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.1% East Asian · 31,882/44,854 alleles

Filtering AF 70.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.2%

Overall 56.2% 907,727/1,613,918 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	71.1%	1
South Asian	67%	1
Admixed American	62.8%	2
Ashkenazi Jewishnot grpmax-eligible	59.9%	2
Finnishnot grpmax-eligible	58.3%	2
Remaining individualsnot grpmax-eligible	57.4%	2
African / African-American	56.8%	2
Middle Eastern	55.2%	2
European (non-Finnish)	54.2%	2
Amishnot grpmax-eligible	48.1%	2

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.Leu324=
Coding: c.970C>T
MANE Select: NM_014974
dbSNP: rs4881274
Type: single nucleotide variant
Location: chr10:414000 (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.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-leu324 (accessed [today's date]).

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