Is DYNLT4 p.Arg29Gln (c.86G>A) pathogenic?

DYNLT4 p.Arg29Gln (c.86G>A) is classified Uncertain significance in DYNLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.085); Very rare (popmax 0.00518%, sas).

How common is DYNLT4 p.Arg29Gln (c.86G>A) in the general population?

DYNLT4 p.Arg29Gln (c.86G>A) is very rare (popmax 0.00518%, sas) (gnomAD).

What do computational predictors say about DYNLT4 p.Arg29Gln (c.86G>A)?

AlphaMissense predicts likely benign (score 0.085) — an in-silico prediction, not a clinical call.

DYNLT4 p.Arg29Gln

c.86G>A · VCV3274218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00518%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.085	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -8.05	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 0.98	GERP -2.1
Regional constraint	o/e 1.01	unconstrained · MANE · 662 bp · p 0.79 · regional, not allelic
Overall
CADD	13.95	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 0.00518% South Asian · 4/77,284 alleles

Filtering AF 0.00171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.00112% 15/1,338,710 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00518%	19,321
European (non-Finnish)	0.00098%	102,080

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: DYNLT4
Protein: p.Arg29Gln
Coding: c.86G>A
MANE Select: NM_001377534
Type: single nucleotide variant
Location: chr1:44806583 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.02
Residue 29: the 'disordered' region

Full DYNLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT4 p.Arg29Pro Likely benign ★ same residue
DYNLT4 p.Ala130Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala195Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala41Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala58Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala72Thr 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/dynlt4-p-arg29gln (accessed [today's date]).

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