Is DIP2C p.Val834Met (c.2500G>A) pathogenic?

DIP2C p.Val834Met (c.2500G>A) is classified Uncertain significance in DIP2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). AlphaMissense: ambiguous (0.5118); Very rare (popmax 0.00432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Val834Met (c.2500G>A)?

DIP2C p.Val834Met (c.2500G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Val834Met (c.2500G>A) in the general population?

DIP2C p.Val834Met (c.2500G>A) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about DIP2C p.Val834Met (c.2500G>A)?

AlphaMissense predicts ambiguous (score 0.5118) — an in-silico prediction, not a clinical call.

DIP2C p.Val834Met

c.2500G>A · VCV4011770

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5118	ambiguous
REVEL	0.317	indeterminate
SaProt	LLR -11.87	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 54 kb · p 2.7e-23 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00432% European (non-Finnish) · 51/1,179,988 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00354% 57/1,611,918 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)grpmax	0.00432%	23,137
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,066

Remaining individuals 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.Val834Met
Coding: c.2500G>A
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:363289 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIP2C p.Ala1066Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1101Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1155Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala1466Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala193Val Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala422Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala71Thr Uncertain significance ★★ ⚠ same condition
DIP2C p.Ala997Val Uncertain significance ★★ ⚠ 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-val834met (accessed [today's date]).

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