Is DIP2C p.Arg62Cys (c.184C>T) pathogenic?

DIP2C p.Arg62Cys (c.184C>T) is classified Conflicting classifications of pathogenicity in DIP2C (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.1696); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Arg62Cys (c.184C>T)?

DIP2C p.Arg62Cys (c.184C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Arg62Cys (c.184C>T) in the general population?

DIP2C p.Arg62Cys (c.184C>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DIP2C p.Arg62Cys (c.184C>T)?

AlphaMissense predicts likely benign (score 0.1696) — an in-silico prediction, not a clinical call.

DIP2C p.Arg62Cys

c.184C>T · VCV3502058

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1696 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1696	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -9.55	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 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 290 kb · p 0.0041 · regional, not allelic
Overall
CADD	29.6	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 0.01% Admixed American · 6/60,006 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00211% 34/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,001
South Asian	0.0022%	45,539
European (non-Finnish)	0.00195%	51,307
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00156%	63,984
African / African-American	0.00133%	74,938

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.Arg62Cys
Coding: c.184C>T
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:472523 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.64
Residue 62: 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

DIP2C p.Arg62His Uncertain significance ★ ⚠ same residue
DIP2C p.Arg62= Likely benign ★ same residue
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

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-arg62cys (accessed [today's date]).

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