Is DYNC2LI1 p.Val114Ile (c.340G>A) pathogenic?

DYNC2LI1 p.Val114Ile (c.340G>A) is classified Uncertain significance in DYNC2LI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-13). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYNC2LI1 p.Val114Ile (c.340G>A)?

DYNC2LI1 p.Val114Ile (c.340G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2LI1 p.Val114Ile (c.340G>A) in the general population?

DYNC2LI1 p.Val114Ile (c.340G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Val114Ile (c.340G>A)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Val114Ile

c.340G>A · rs776935418 · VCV2528727

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.2	GERP 0.71, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	16.61	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 0.0178% East Asian · 8/44,854 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00409% 66/1,612,414 alleles · ultra-rare exomes 60/1,460,506 · genomes 6/151,908 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,607
Remaining individualsnot grpmax-eligible	0.00481%	20,810
European (non-Finnish)	0.00424%	23,588
African / African-American	0.00402%	24,895
South Asian	0.0022%	45,466

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.Val114Ile
Coding: c.340G>A
MANE Select: NM_016008
dbSNP: rs776935418
Type: single nucleotide variant
Location: chr2:43794476 (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.Asp95Ala Benign/Likely benign ★★ 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-val114ile (accessed [today's date]).

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