Is DIP2A p.Leu693= (c.2079G>A) pathogenic?

DIP2A p.Leu693= (c.2079G>A) is classified Benign in DIP2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-18). Common (popmax 50.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DIP2A-related disorder.

What condition is associated with DIP2A p.Leu693= (c.2079G>A)?

DIP2A p.Leu693= (c.2079G>A) is associated with DIP2A-related disorder (ClinVar).

DIP2A p.Leu693=

Q: How common is DIP2A p.Leu693= (c.2079G>A) in the general population?

DIP2A p.Leu693= (c.2079G>A) is common (popmax 50.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2079G>A · rs2070435 · VCV3060508

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 50.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DIP2A-related disorder

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 -1.9	GERP -4.2
Overall
CADD	0.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.2% African / African-American · 37,573/74,906 alleles

Filtering AF 49.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.6%

Overall 33.2% 534,910/1,613,500 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	50.2%	2
East Asian	43.6%	2
Amishnot grpmax-eligible	41.7%	2
Middle Eastern	38.4%	3
Remaining individualsnot grpmax-eligible	34.2%	3
European (non-Finnish)	32.3%	3
South Asian	32%	3
Finnishnot grpmax-eligible	30.7%	3
Ashkenazi Jewishnot grpmax-eligible	29.6%	3
Admixed American	24.3%	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: DIP2A
Protein: p.Leu693=
Coding: c.2079G>A
MANE Select: NM_015151
dbSNP: rs2070435
Type: single nucleotide variant
Location: chr21:46541798 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93

Full DIP2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2A-related disorder

Similar variants

DIP2A p.Ala1026Ser Uncertain significance ★ ⚠ same condition
DIP2A c.2637+25G>T Uncertain significance same condition
DIP2A p.Ala1260Ser Uncertain significance ⚠ same condition
DIP2A p.Arg602Trp Uncertain significance ⚠ same condition
DIP2A p.Glu63Asp Uncertain significance ⚠ same condition
DIP2A p.Lys281Thr Uncertain significance ⚠ same condition
DIP2A p.Ser1249Cys Uncertain significance ⚠ same condition
DIP2A c.1707+7G>A Likely benign same condition

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/dip2a-p-leu693 (accessed [today's date]).

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