Is DIP2C p.Ala739= (c.2217G>A) pathogenic?

DIP2C p.Ala739= (c.2217G>A) is classified Likely benign in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). Ultra-rare (popmax 0.0164%, mid).

How common is DIP2C p.Ala739= (c.2217G>A) in the general population?

DIP2C p.Ala739= (c.2217G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

DIP2C p.Ala739=

c.2217G>A · rs756845585 · VCV1596217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -3.7
Overall
CADD	0.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00316% 51/1,613,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0187%	5,336
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00667%	14,984
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.00439%	22,761
Admixed American	0.00333%	29,990
European (non-Finnish)	0.00195%	51,304

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala739=
Coding: c.2217G>A
MANE Select: NM_014974
dbSNP: rs756845585
Type: single nucleotide variant
Location: chr10:366326 (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-ala739 (accessed [today's date]).

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