Is DIP2A p.Pro58= (c.174A>G) pathogenic?

DIP2A p.Pro58= (c.174A>G) is classified Benign in DIP2A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-15). Common (popmax 47.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DIP2A-related disorder.

What condition is associated with DIP2A p.Pro58= (c.174A>G)?

DIP2A p.Pro58= (c.174A>G) is associated with DIP2A-related disorder (ClinVar).

DIP2A p.Pro58=

Q: How common is DIP2A p.Pro58= (c.174A>G) in the general population?

DIP2A p.Pro58= (c.174A>G) is common (popmax 47.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.174A>G · rs7279002 · VCV3060043

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 47.2%, 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 -5.1	GERP -4.7
Overall
CADD	3.336	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.2% African / African-American · 34,778/73,746 alleles

Filtering AF 46.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.6%

Overall 25.7% 401,864/1,566,230 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	47.2%	2
East Asian	43.7%	2
Middle Eastern	34%	3
Amishnot grpmax-eligible	33%	3
South Asian	31%	3
Remaining individualsnot grpmax-eligible	27.8%	4
Finnishnot grpmax-eligible	27.2%	4
Ashkenazi Jewishnot grpmax-eligible	25.8%	4
European (non-Finnish)	23.2%	4
Admixed American	21.1%	5

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.Pro58=
Coding: c.174A>G
MANE Select: NM_015151
dbSNP: rs7279002
Type: single nucleotide variant
Location: chr21:46490610 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93
Residue 58: the dmap1-binding domain

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-pro58 (accessed [today's date]).

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