Is DYNC2LI1 p.Val272Phe (c.814G>T) pathogenic?

DYNC2LI1 p.Val272Phe (c.814G>T) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0941); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYNC2LI1 p.Val272Phe (c.814G>T)?

DYNC2LI1 p.Val272Phe (c.814G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2LI1 p.Val272Phe (c.814G>T) in the general population?

DYNC2LI1 p.Val272Phe (c.814G>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Val272Phe (c.814G>T)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Val272Phe

c.814G>T · VCV4618170

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.74	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 1.1	GERP -2.3, phastCons 0.94
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	13.81	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 0.0112% East Asian · 5/44,676 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.000374% 6/1,603,260 alleles · ultra-rare exomes 4/1,451,124 · genomes 2/152,136 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,935
Admixed American	0.00173%	57,702

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.Val272Phe
Coding: c.814G>T
MANE Select: NM_016008
Type: single nucleotide variant
Location: chr2:43804653 (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.Val114Ile Uncertain significance ★★ ⚠ 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-val272phe (accessed [today's date]).

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