Is DYNC2LI1 p.Pro176Leu (c.527C>T) pathogenic?

DYNC2LI1 p.Pro176Leu (c.527C>T) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.1712); Very rare (popmax 0.00223%, eas).

How common is DYNC2LI1 p.Pro176Leu (c.527C>T) in the general population?

DYNC2LI1 p.Pro176Leu (c.527C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Pro176Leu (c.527C>T)?

AlphaMissense predicts likely benign (score 0.1712) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Pro176Leu

c.527C>T · rs1004100307 · VCV2126866

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1712	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	28.5	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 0.00223% East Asian · 1/44,820 alleles

Overall 0.000124% 2/1,612,992 alleles · very rare exomes 2/1,460,742 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,820
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Pro176Leu
Coding: c.527C>T
MANE Select: NM_016008
dbSNP: rs1004100307
Type: single nucleotide variant
Location: chr2:43795909 (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-pro176leu (accessed [today's date]).

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