Is DIP2C p.Arg78Trp (c.232C>T) pathogenic?

DIP2C p.Arg78Trp (c.232C>T) is classified Uncertain significance in DIP2C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-27). AlphaMissense: likely pathogenic (0.6694); Very rare (popmax 0.00373%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Arg78Trp (c.232C>T)?

DIP2C p.Arg78Trp (c.232C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Arg78Trp (c.232C>T) in the general population?

DIP2C p.Arg78Trp (c.232C>T) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about DIP2C p.Arg78Trp (c.232C>T)?

AlphaMissense predicts likely pathogenic (score 0.6694) — an in-silico prediction, not a clinical call.

DIP2C p.Arg78Trp

c.232C>T · rs373914983 · VCV2519640

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6694	likely pathogenic
REVEL	0.434	indeterminate
SaProt	LLR -10.56	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP -3.4, phastCons 0.29
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	23.2	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 0.00373% European (non-Finnish) · 44/1,180,046 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00291% 47/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,819
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00133%	74,932

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.Arg78Trp
Coding: c.232C>T
MANE Select: NM_014974
dbSNP: rs373914983
Type: single nucleotide variant
Location: chr10:472475 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 78: the dmap1-binding domain; the 'disordered' region

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

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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-arg78trp (accessed [today's date]).

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