Is DYNC2LI1 p.Asp95Ala (c.284A>C) pathogenic?

DYNC2LI1 p.Asp95Ala (c.284A>C) is classified Benign/Likely benign in DYNC2LI1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). AlphaMissense: ambiguous (0.3997); Low-frequency (popmax 1.38%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2LI1 p.Asp95Ala (c.284A>C)?

DYNC2LI1 p.Asp95Ala (c.284A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2LI1 p.Asp95Ala (c.284A>C) in the general population?

DYNC2LI1 p.Asp95Ala (c.284A>C) is low-frequency (popmax 1.38%, afr) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Asp95Ala (c.284A>C)?

AlphaMissense predicts ambiguous (score 0.3997) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Asp95Ala

c.284A>C · rs142464485 · VCV716068

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3997 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3997	ambiguous
REVEL	0.533	indeterminate
SaProt	LLR -11.22	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	26.4	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 1.38% African / African-American · 1,036/75,028 alleles

Filtering AF 1.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.28%

Overall 0.0727% 1,173/1,613,924 alleles · low-frequency exomes 619/1,461,654 · genomes 554/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.38%	72
Admixed American	0.0867%	1,154
Remaining individualsnot grpmax-eligible	0.0816%	1,226
Middle Eastern	0.066%	1,516
South Asian	0.00439%	22,761
European (non-Finnish)	0.0022%	45,381

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: DYNC2LI1
Protein: p.Asp95Ala
Coding: c.284A>C
MANE Select: NM_016008
dbSNP: rs142464485
Type: single nucleotide variant
Location: chr2:43789685 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 3 PDB

Full DYNC2LI1 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

DYNC2LI1 p.Cys203Tyr Uncertain significance ★★ same condition
DYNC2LI1 p.Glu23Lys Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Gly24Asp Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Gly88Ser Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Ile184Thr Uncertain significance ★★ same condition
DYNC2LI1 p.Pro254Leu Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Tyr213Cys Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Val114Ile 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/dync2li1-p-asp95ala (accessed [today's date]).

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