Is DYNC1LI2 p.Asp351Asn (c.1051G>A) pathogenic?

DYNC1LI2 p.Asp351Asn (c.1051G>A) is classified Uncertain significance in DYNC1LI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-30). AlphaMissense: likely benign (0.3136); Very rare (popmax 0.00271%, nfe).

How common is DYNC1LI2 p.Asp351Asn (c.1051G>A) in the general population?

DYNC1LI2 p.Asp351Asn (c.1051G>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about DYNC1LI2 p.Asp351Asn (c.1051G>A)?

AlphaMissense predicts likely benign (score 0.3136) — an in-silico prediction, not a clinical call.

DYNC1LI2 p.Asp351Asn

c.1051G>A · rs749334921 · VCV2221088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3136	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 28 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	30.0	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 0.00271% European (non-Finnish) · 32/1,180,054 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00223% 36/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)grpmax	0.00271%	36,877
African / African-American	0.00267%	37,461

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DYNC1LI2
Protein: p.Asp351Asn
Coding: c.1051G>A
MANE Select: NM_006141
dbSNP: rs749334921
Type: single nucleotide variant
Location: chr16:66729090 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 24 PDB
Residue 351: an α-helix

Full DYNC1LI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC1LI2 p.Ala122Ser Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala153Gly Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala22Val Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg103Cys Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157Cys Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157His Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg175Gln Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg397Trp 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/dync1li2-p-asp351asn (accessed [today's date]).

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