Is DYNLT3 p.Ala45Val (c.134C>T) pathogenic?

DYNLT3 p.Ala45Val (c.134C>T) is classified Uncertain significance in DYNLT3 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.6911); Very rare (popmax 0.00222%, amr).

How common is DYNLT3 p.Ala45Val (c.134C>T) in the general population?

DYNLT3 p.Ala45Val (c.134C>T) is very rare (popmax 0.00222%, amr) (gnomAD).

What do computational predictors say about DYNLT3 p.Ala45Val (c.134C>T)?

AlphaMissense predicts likely pathogenic (score 0.6911) — an in-silico prediction, not a clinical call.

DYNLT3 p.Ala45Val

c.134C>T · rs1930168328 · VCV3086568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6911	likely pathogenic
REVEL	0.204	benign-leaning
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 0.98, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 6,932 bp · p 0.99 · regional, not allelic
Overall
CADD	27.0	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 0.00222% Admixed American · 1/45,027 alleles

Overall 8.57e-05% 1/1,166,599 alleles · very rare exomes 0/1,055,661 · genomes 1/110,938 · joint denominator

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: DYNLT3
Protein: p.Ala45Val
Coding: c.134C>T
MANE Select: NM_006520
dbSNP: rs1930168328
Type: single nucleotide variant
Location: chrX:37841844 (GRCh38)
Structure: AlphaFold pLDDT 90.46

Full DYNLT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT3 p.Ala61= Benign ★★ same type
DYNLT3 p.Ala75Thr Uncertain significance ★ ⚠ same type
DYNLT3 p.Arg101Trp Uncertain significance ★ same type
DYNLT3 p.Arg6Gly Uncertain significance ★ ⚠ same type
DYNLT3 p.Gln42Glu Uncertain significance ★ ⚠ same type
DYNLT3 p.His7Arg Uncertain significance ★ ⚠ same type
DYNLT3 p.Leu116Ile Uncertain significance ★ ⚠ same type
DYNLT3 p.Thr88Ile 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/dynlt3-p-ala45val (accessed [today's date]).

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