Is DYNLT5 p.Leu167Pro (c.500T>C) pathogenic?

DYNLT5 p.Leu167Pro (c.500T>C) is classified Uncertain significance in DYNLT5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely pathogenic (0.9418); Absent from gnomAD v4.1.

How common is DYNLT5 p.Leu167Pro (c.500T>C) in the general population?

DYNLT5 p.Leu167Pro (c.500T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNLT5 p.Leu167Pro (c.500T>C)?

AlphaMissense predicts likely pathogenic (score 0.9418) — an in-silico prediction, not a clinical call.

DYNLT5 p.Leu167Pro

c.500T>C · rs2549208222 · VCV3086594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9418 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9418	likely pathogenic · top 1% in DYNLT5
REVEL	0.635	indeterminate
SaProt	LLR -16.57	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 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 23 kb · p 0.34 · regional, not allelic
Overall
CADD	26.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNLT5
Protein: p.Leu167Pro
Coding: c.500T>C
MANE Select: NM_152665
dbSNP: rs2549208222
Type: single nucleotide variant
Location: chr1:66777414 (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-leu167pro (accessed [today's date]).

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