Is DYNC2LI1 p.Arg231Cys (c.691C>T) pathogenic?

DYNC2LI1 p.Arg231Cys (c.691C>T) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.62); Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with DYNC2LI1 p.Arg231Cys (c.691C>T)?

DYNC2LI1 p.Arg231Cys (c.691C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2LI1 p.Arg231Cys (c.691C>T) in the general population?

DYNC2LI1 p.Arg231Cys (c.691C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Arg231Cys (c.691C>T)?

AlphaMissense predicts likely pathogenic (score 0.62) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Arg231Cys

c.691C>T · VCV3843072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.62 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.62	likely pathogenic
REVEL	0.376	indeterminate
SaProt	LLR -13.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.21	acceptor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.31	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0166% Middle Eastern · 1/6,028 alleles

Filtering AF 0.00472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00433%

Overall 0.00468% 75/1,603,374 alleles · ultra-rare exomes 72/1,451,534 · genomes 3/151,840 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,028
European (non-Finnish)	0.00588%	17,016
Remaining individualsnot grpmax-eligible	0.00323%	30,990
East Asian	0.00225%	44,528
African / African-American	0.00134%	74,490
South Asian	0.00111%	89,796

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.Arg231Cys
Coding: c.691C>T
MANE Select: NM_016008
Type: single nucleotide variant
Location: chr2:43800877 (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-arg231cys (accessed [today's date]).

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