Is DYNC2H1 p.Ala195Val (c.584C>T) pathogenic?

DYNC2H1 p.Ala195Val (c.584C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-14). AlphaMissense: likely pathogenic (0.5672); Rare (popmax 0.251%, eas).

How common is DYNC2H1 p.Ala195Val (c.584C>T) in the general population?

DYNC2H1 p.Ala195Val (c.584C>T) is rare (popmax 0.251%, eas) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala195Val (c.584C>T)?

AlphaMissense predicts likely pathogenic (score 0.5672) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala195Val

c.584C>T · VCV4913662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5672 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.251%, eas)

Computational evidence

Protein change
AlphaMissense	0.5672	likely pathogenic
REVEL	0.33	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.251% East Asian · 112/44,588 alleles

Filtering AF 0.213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.199%

Overall 0.00917% 147/1,602,610 alleles · rare exomes 137/1,450,518 · genomes 10/152,092 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.251%	398
South Asian	0.0294%	3,405
Remaining individualsnot grpmax-eligible	0.0129%	7,760
European (non-Finnish)	8.52e-05%	1,174,180

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: DYNC2H1
Protein: p.Ala195Val
Coding: c.584C>T
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103115258 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 195: the 'stem' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC2H1 p.Ala195= Likely benign ★ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same type
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same type
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ 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/dync2h1-p-ala195val (accessed [today's date]).

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