Is DYNC2LI1 p.Pro285Thr (c.853C>A) pathogenic?

DYNC2LI1 p.Pro285Thr (c.853C>A) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.2589); Very rare (popmax 0.0017%, amr).

How common is DYNC2LI1 p.Pro285Thr (c.853C>A) in the general population?

DYNC2LI1 p.Pro285Thr (c.853C>A) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Pro285Thr (c.853C>A)?

AlphaMissense predicts likely benign (score 0.2589) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Pro285Thr

c.853C>A · rs780816640 · VCV1957492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2589	likely benign
REVEL	0.536	indeterminate
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,722 alleles

Overall 0.000124% 2/1,607,930 alleles · very rare exomes 2/1,455,688 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,722
South Asian	0.00112%	89,338

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.Pro285Thr
Coding: c.853C>A
MANE Select: NM_016008
dbSNP: rs780816640
Type: single nucleotide variant
Location: chr2:43804692 (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

Similar variants

DYNC2LI1 p.Leu117Val Pathogenic/Likely pathogenic ★★ ⚠ same type
DYNC2LI1 p.Trp124Ter Pathogenic/Likely pathogenic ★★ same type
ABCG5 p.Ala505Asp Uncertain significance ★★ ⚠ same type
ABCG5 p.Gly288Ser Uncertain significance ★★ ⚠ same type
ABCG5 p.Ser361Cys Uncertain significance ★★ ⚠ same type
ABCG5 p.Val420Gly Uncertain significance ★★ ⚠ same type
DYNC2LI1 p.Cys203Tyr Uncertain significance ★★ same type
DYNC2LI1 p.Glu23Lys 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/dync2li1-p-pro285thr (accessed [today's date]).

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