Is DYNC1LI2 p.Met185Val (c.553A>G) pathogenic?

DYNC1LI2 p.Met185Val (c.553A>G) is classified Likely benign in DYNC1LI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely benign (0.0447); Rare (popmax 0.397%, eas).

How common is DYNC1LI2 p.Met185Val (c.553A>G) in the general population?

DYNC1LI2 p.Met185Val (c.553A>G) is rare (popmax 0.397%, eas) (gnomAD).

What do computational predictors say about DYNC1LI2 p.Met185Val (c.553A>G)?

AlphaMissense predicts likely benign (score 0.0447) — an in-silico prediction, not a clinical call.

DYNC1LI2 p.Met185Val

c.553A>G · VCV4662670

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0447 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.397%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0447	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -5.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.8
Regional constraint	o/e 0.78	unconstrained · MANE · 28 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	0.05	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 0.397% East Asian · 178/44,872 alleles

Filtering AF 0.349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.0115% 186/1,613,836 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.397%	252
Admixed American	0.00167%	59,942
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	0.000509%	196,643

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.Met185Val
Coding: c.553A>G
MANE Select: NM_006141
Type: single nucleotide variant
Location: chr16:66736221 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 24 PDB
Residue 185: a β-strand

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-met185val (accessed [today's date]).

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