Is DIP2C p.Ser142Ala (c.424T>G) pathogenic?

DIP2C p.Ser142Ala (c.424T>G) is classified Uncertain significance in DIP2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.0739); Very rare (popmax 8.48e-05%, nfe); Associated with DIP2C-related disorder.

What condition is associated with DIP2C p.Ser142Ala (c.424T>G)?

DIP2C p.Ser142Ala (c.424T>G) is associated with DIP2C-related disorder (ClinVar).

How common is DIP2C p.Ser142Ala (c.424T>G) in the general population?

DIP2C p.Ser142Ala (c.424T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DIP2C p.Ser142Ala (c.424T>G)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

DIP2C p.Ser142Ala

c.424T>G · rs1966309744 · VCV2631191

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIP2C-related disorder

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.48e-05% European (non-Finnish) · 1/1,178,848 alleles

Overall 0.000657% 1/152,188 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.Ser142Ala
Coding: c.424T>G
MANE Select: NM_014974
dbSNP: rs1966309744
Type: single nucleotide variant
Location: chr10:423004 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 142: the 'disordered' region

Full DIP2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIP2C-related disorder

Similar variants

DIP2C c.2268+1G>A Likely pathogenic ★ same condition
DIP2C p.Arg1539Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
DIP2C p.Arg77= Uncertain significance ★ same condition
DIP2C p.Val1440Ile Uncertain significance ★ ⚠ same condition
DIP2C p.Thr501Ser Uncertain significance ⚠ same condition
DIP2C p.Val1105Phe Uncertain significance ⚠ same condition
DIP2C c.1385-4C>T Likely benign same condition
DIP2C p.Leu1137= 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/dip2c-p-ser142ala (accessed [today's date]).

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