Is DCTN2 p.Asp168Val (c.503A>T) pathogenic?

DCTN2 p.Asp168Val (c.503A>T) is classified Uncertain significance in DCTN2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.822); Absent from gnomAD v4.1.

How common is DCTN2 p.Asp168Val (c.503A>T) in the general population?

DCTN2 p.Asp168Val (c.503A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCTN2 p.Asp168Val (c.503A>T)?

AlphaMissense predicts likely pathogenic (score 0.822) — an in-silico prediction, not a clinical call.

DCTN2 p.Asp168Val

c.503A>T · rs2140121175 · VCV1330219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.822	likely pathogenic
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 3,651 bp · p 0.083 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCTN2
Protein: p.Asp168Val
Coding: c.503A>T
MANE Select: NM_001261413
dbSNP: rs2140121175
Type: single nucleotide variant
Location: chr12:57534313 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 2 PDB
Residue 168: an α-helix

Full DCTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCTN2 c.1119+7G>A Uncertain significance ★ same type
DCTN2 p.Ala162Gly Uncertain significance ★ ⚠ same type
DCTN2 p.Ala7Ser Uncertain significance ★ ⚠ same type
DCTN2 p.Arg332Ile Uncertain significance ★ ⚠ same type
DCTN2 p.Arg379Cys Conflicting classifications of pathogenicity ★ ⚠ same type
DCTN2 p.Arg395Gln Uncertain significance ★ ⚠ same type
DCTN2 p.Asp216Asn Uncertain significance ★ ⚠ same type
DCTN2 p.Asp216Glu Uncertain significance ★ ⚠ same type

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/dctn2-p-asp168val (accessed [today's date]).

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