Is DIP2C p.Ala1304Val (c.3911C>T) pathogenic?

DIP2C p.Ala1304Val (c.3911C>T) is classified Uncertain significance in DIP2C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). AlphaMissense: likely pathogenic (0.8521); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DIP2C p.Ala1304Val (c.3911C>T)?

DIP2C p.Ala1304Val (c.3911C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DIP2C p.Ala1304Val (c.3911C>T) in the general population?

DIP2C p.Ala1304Val (c.3911C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DIP2C p.Ala1304Val (c.3911C>T)?

AlphaMissense predicts likely pathogenic (score 0.8521) — an in-silico prediction, not a clinical call.

DIP2C p.Ala1304Val

c.3911C>T · VCV3502069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8521	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 68 kb · p 3e-19 · regional, not allelic
Overall
CADD	29.2	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 0.00223% East Asian · 1/44,888 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,612,826 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
Remaining individualsnot grpmax-eligible	0.0016%	62,424
South Asian	0.0011%	90,916
European (non-Finnish)	0.000339%	294,874

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.Ala1304Val
Coding: c.3911C>T
MANE Select: NM_014974
Type: single nucleotide variant
Location: chr10:327019 (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.Ala1304= 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
DIP2C p.Ala71Thr 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-ala1304val (accessed [today's date]).

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