Is DYNLT2 p.Ala164Val (c.491C>T) pathogenic?

DYNLT2 p.Ala164Val (c.491C>T) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.2919); Rare (popmax 0.101%, afr).

How common is DYNLT2 p.Ala164Val (c.491C>T) in the general population?

DYNLT2 p.Ala164Val (c.491C>T) is rare (popmax 0.101%, afr) (gnomAD).

What do computational predictors say about DYNLT2 p.Ala164Val (c.491C>T)?

AlphaMissense predicts likely benign (score 0.2919) — an in-silico prediction, not a clinical call.

DYNLT2 p.Ala164Val

c.491C>T · rs375109366 · VCV3086562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2919 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2919	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.81	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 5.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	21.3	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 0.101% African / African-American · 76/74,890 alleles

Filtering AF 0.083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.00547% 88/1,609,794 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	985
Admixed American	0.0117%	8,551
Remaining individualsnot grpmax-eligible	0.00481%	20,790
European (non-Finnish)	0.00017%	588,318

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.Ala164Val
Coding: c.491C>T
MANE Select: NM_174910
dbSNP: rs375109366
Type: single nucleotide variant
Location: chr6:169740291 (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.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
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-ala164val (accessed [today's date]).

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