Is DIP2C p.Ala737fs (c.2208_2209dup) pathogenic?

DIP2C p.Ala737fs (c.22082209dup) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-21). Very rare (popmax 8.48e-05%, nfe); Associated with neurodevelopmental disorder.

What condition is associated with DIP2C p.Ala737fs (c.2208_2209dup)?

DIP2C p.Ala737fs (c.2208_2209dup) is associated with neurodevelopmental disorder (ClinVar).

How common is DIP2C p.Ala737fs (c.2208_2209dup) in the general population?

DIP2C p.Ala737fs (c.2208_2209dup) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DIP2C p.Ala737fs

c.2208_2209dup · rs779890829 · VCV1321981

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 19 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,924 alleles

Overall 6.84e-05% 1/1,461,648 alleles · very rare

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.Ala737fs
Coding: c.2208_2209dup
MANE Select: NM_014974
dbSNP: rs779890829
Type: Microsatellite
Location: chr10:366333 (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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIP2C p.Ala737Ser Uncertain significance ★ ⚠ same residue
DIP2C p.Asn390fs Likely pathogenic ★ same condition
DIP2C p.Arg1253Ter Conflicting classifications of pathogenicity ★ same condition
DIP2C p.Tyr1438Ter Uncertain significance ★ same condition
DIP2C p.Tyr745fs Uncertain significance ★ same condition
DIP2C p.Ser612fs Pathogenic ★ same type
DIP2C p.Ala1043del Uncertain significance ★ same type
DIP2C p.Ala1102_Val1103insAla 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-ala737fs (accessed [today's date]).

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