Is DIP2C p.Ala495Glu (c.1484C>A) pathogenic?

DIP2C p.Ala495Glu (c.1484C>A) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). AlphaMissense: likely pathogenic (0.9959); Very rare (popmax 0.00144%, nfe).

How common is DIP2C p.Ala495Glu (c.1484C>A) in the general population?

DIP2C p.Ala495Glu (c.1484C>A) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about DIP2C p.Ala495Glu (c.1484C>A)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

DIP2C p.Ala495Glu

c.1484C>A · rs370308829 · VCV2413626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic · top 6% in DIP2C
REVEL	0.744	pathogenic-leaning
SaProt	LLR -15.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 54 kb · p 2.7e-23 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,179,930 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,613,748 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00144%	69,408
South Asian	0.0011%	91,048

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.Ala495Glu
Coding: c.1484C>A
MANE Select: NM_014974
dbSNP: rs370308829
Type: single nucleotide variant
Location: chr10:390274 (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.Ala495Thr Uncertain significance ★ ⚠ same residue
DIP2C p.Ala495Val Uncertain significance ★ ⚠ same residue
DIP2C p.Ala495= Likely benign ★ same residue
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

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-ala495glu (accessed [today's date]).

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