Is DYNC2LI1 p.Glu348Gln (c.1042G>C) pathogenic?

DYNC2LI1 p.Glu348Gln (c.1042G>C) is classified Benign/Likely benign in DYNC2LI1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1184); Rare (popmax 0.135%, mid).

How common is DYNC2LI1 p.Glu348Gln (c.1042G>C) in the general population?

DYNC2LI1 p.Glu348Gln (c.1042G>C) is rare (popmax 0.135%, mid) (gnomAD).

What do computational predictors say about DYNC2LI1 p.Glu348Gln (c.1042G>C)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Glu348Gln

c.1042G>C · rs41281457 · VCV777768

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.1	GERP 1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	17.03	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 0.135% Middle Eastern · 8/5,916 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.15% 2,421/1,611,624 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.71%	37
Remaining individualsnot grpmax-eligible	0.337%	297
Middle Easterngrpmax	0.135%	739
European (non-Finnish)	0.112%	896
Admixed American	0.0753%	1,328
African / African-American	0.032%	3,123
South Asian	0.011%	9,061
Finnishnot grpmax-eligible	0.0109%	9,138

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu348Gln
Coding: c.1042G>C
MANE Select: NM_022436 · reported on NM_016008
dbSNP: rs41281457
Type: single nucleotide variant
Location: chr2:43809753 (GRCh38)

Full DYNC2LI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-glu348gln (accessed [today's date]).

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