Is DYNLT2 p.Ala23Ser (c.67G>T) pathogenic?

DYNLT2 p.Ala23Ser (c.67G>T) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0674); Ultra-rare (popmax 0.033%, mid).

How common is DYNLT2 p.Ala23Ser (c.67G>T) in the general population?

DYNLT2 p.Ala23Ser (c.67G>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DYNLT2 p.Ala23Ser (c.67G>T)?

AlphaMissense predicts likely benign (score 0.0674) — an in-silico prediction, not a clinical call.

DYNLT2 p.Ala23Ser

c.67G>T · VCV4245893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0674 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0674	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.5	GERP -4.3
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	0.219	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00304% 49/1,614,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Admixed American	0.015%	6,670
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.00266%	37,531
European (non-Finnish)	0.00229%	43,704

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.Ala23Ser
Coding: c.67G>T
MANE Select: NM_018341 · reported on NM_174910
Type: single nucleotide variant
Location: chr6:169751392 (GRCh38)

Full DYNLT2 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/dynlt2-p-ala23ser (accessed [today's date]).

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