Is DYNLT5 p.Ser166Pro (c.496T>C) pathogenic?

DYNLT5 p.Ser166Pro (c.496T>C) is classified Uncertain significance in DYNLT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely pathogenic (0.8088); Very rare (popmax 0.00133%, afr).

How common is DYNLT5 p.Ser166Pro (c.496T>C) in the general population?

DYNLT5 p.Ser166Pro (c.496T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DYNLT5 p.Ser166Pro (c.496T>C)?

AlphaMissense predicts likely pathogenic (score 0.8088) — an in-silico prediction, not a clinical call.

DYNLT5 p.Ser166Pro

c.496T>C · VCV4662689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8088	likely pathogenic · top 7% in DYNLT5
REVEL	0.386	indeterminate
SaProt	LLR -13.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 23 kb · p 0.34 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,038 alleles

Overall 6.84e-05% 1/1,461,566 alleles · very rare

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: DYNLT5
Protein: p.Ser166Pro
Coding: c.496T>C
MANE Select: NM_152665
Type: single nucleotide variant
Location: chr1:66777410 (GRCh38)
Gene constraint: LOEUF 1.657 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.94

Full DYNLT5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT5 p.Ala169Ser Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg125Gln Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg125Trp Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg37His Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg54Cys Uncertain significance ★ ⚠ same type
DYNLT5 p.Arg54His Uncertain significance ★ ⚠ same type
DYNLT5 p.Asn26His Uncertain significance ★ ⚠ same type
DYNLT5 p.Asn6Lys 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/dynlt5-p-ser166pro (accessed [today's date]).

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