Is DYNLT1 p.Ile29Val (c.85A>G) pathogenic?

DYNLT1 p.Ile29Val (c.85A>G) is classified Uncertain significance in DYNLT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1107); Ultra-rare (popmax 0.029%, eas).

How common is DYNLT1 p.Ile29Val (c.85A>G) in the general population?

DYNLT1 p.Ile29Val (c.85A>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DYNLT1 p.Ile29Val (c.85A>G)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

DYNLT1 p.Ile29Val

c.85A>G · rs375535915 · VCV2461130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -8.37	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	GERP 0.69, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,878 bp · p 0.84 · regional, not allelic
Overall
CADD	23.3	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 0.029% East Asian · 13/44,900 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.002% 32/1,603,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,454
Remaining individualsnot grpmax-eligible	0.0016%	62,436
European (non-Finnish)	0.00144%	69,411
African / African-American	0.00133%	74,918

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: DYNLT1
Protein: p.Ile29Val
Coding: c.85A>G
MANE Select: NM_006519
dbSNP: rs375535915
Type: single nucleotide variant
Location: chr6:158637879 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 14 PDB
Residue 29: an α-helix

Full DYNLT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT1 p.Ala33Thr Uncertain significance ★ ⚠ same type
DYNLT1 p.Asp90Asn Uncertain significance ★ ⚠ same type
DYNLT1 p.Gln5Glu Uncertain significance ★ ⚠ same type
DYNLT1 p.Glu26Gly Uncertain significance ★ ⚠ same type
DYNLT1 p.Ile105Met Uncertain significance ★ ⚠ same type
DYNLT1 p.Ile113Val Uncertain significance ★ ⚠ same type
DYNLT1 p.Ile20Thr Uncertain significance ★ ⚠ same type
DYNLT1 p.Ile25Met 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/dynlt1-p-ile29val (accessed [today's date]).

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