Is DYNLT2 p.Ala84Ser (c.250G>T) pathogenic?

DYNLT2 p.Ala84Ser (c.250G>T) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.2016); Ultra-rare (popmax 0.084%, afr).

How common is DYNLT2 p.Ala84Ser (c.250G>T) in the general population?

DYNLT2 p.Ala84Ser (c.250G>T) is ultra-rare (popmax 0.084%, afr) (gnomAD).

What do computational predictors say about DYNLT2 p.Ala84Ser (c.250G>T)?

AlphaMissense predicts likely benign (score 0.2016) — an in-silico prediction, not a clinical call.

DYNLT2 p.Ala84Ser

c.250G>T · rs147456843 · VCV3086559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.084%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2016	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 3.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.084% African / African-American · 63/75,022 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.00415% 67/1,613,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.084%	1,191
Remaining individualsnot grpmax-eligible	0.0048%	20,831
Admixed American	0.00167%	60,006

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.Ala84Ser
Coding: c.250G>T
MANE Select: NM_174910
dbSNP: rs147456843
Type: single nucleotide variant
Location: chr6:169744145 (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.Arg132Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144His Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg28Gly 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-ala84ser (accessed [today's date]).

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