Is DYNLT2 p.Glu39Lys (c.115G>A) pathogenic?

DYNLT2 p.Glu39Lys (c.115G>A) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: ambiguous (0.3813); Very rare (popmax 0.00891%, eas).

How common is DYNLT2 p.Glu39Lys (c.115G>A) in the general population?

DYNLT2 p.Glu39Lys (c.115G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DYNLT2 p.Glu39Lys (c.115G>A)?

AlphaMissense predicts ambiguous (score 0.3813) — an in-silico prediction, not a clinical call.

DYNLT2 p.Glu39Lys

c.115G>A · VCV3274212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3813	ambiguous
REVEL	0.15	moderately benign-leaning
SaProt	LLR -6.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 3.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	28.3	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 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,461,564 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
European (non-Finnish)	8.48e-05%	1,179,920

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: DYNLT2
Protein: p.Glu39Lys
Coding: c.115G>A
MANE Select: NM_174910
Type: single nucleotide variant
Location: chr6:169751344 (GRCh38)
Gene constraint: LOEUF 1.376 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.20

Full DYNLT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT2 p.Ala130Val Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala164Val Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala178Thr Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala68Thr Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala84Ser Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg132Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144His 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/dynlt2-p-glu39lys (accessed [today's date]).

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