Is DYNC1LI2 p.Arg103Cys (c.307C>T) pathogenic?

DYNC1LI2 p.Arg103Cys (c.307C>T) is classified Uncertain significance in DYNC1LI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.2617); Very rare (popmax 0.004%, afr).

How common is DYNC1LI2 p.Arg103Cys (c.307C>T) in the general population?

DYNC1LI2 p.Arg103Cys (c.307C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DYNC1LI2 p.Arg103Cys (c.307C>T)?

AlphaMissense predicts likely benign (score 0.2617) — an in-silico prediction, not a clinical call.

DYNC1LI2 p.Arg103Cys

c.307C>T · rs762198514 · VCV2597633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2617 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2617	likely benign
REVEL	0.669	pathogenic-leaning
SaProt	LLR -12.64	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 28 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	33.0	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 0.004% African / African-American · 3/74,918 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000805% 13/1,613,910 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
Admixed American	0.00333%	29,987
Remaining individualsnot grpmax-eligible	0.0032%	31,236
South Asian	0.0011%	91,064
European (non-Finnish)	0.000424%	235,991

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: DYNC1LI2
Protein: p.Arg103Cys
Coding: c.307C>T
MANE Select: NM_006141
dbSNP: rs762198514
Type: single nucleotide variant
Location: chr16:66742660 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 24 PDB
Residue 103: a β-strand

Full DYNC1LI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC1LI2 p.Ala122Ser Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala153Gly Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala22Val Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157Cys Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157His Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg175Gln Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg397Trp Uncertain significance ★ same type
DYNC1LI2 p.Arg477Gln 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/dync1li2-p-arg103cys (accessed [today's date]).

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