Is DYNLT4 p.Arg117Pro (c.350G>C) pathogenic?

DYNLT4 p.Arg117Pro (c.350G>C) is classified Uncertain significance in DYNLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1449); Very rare (popmax 0.000178%, nfe).

How common is DYNLT4 p.Arg117Pro (c.350G>C) in the general population?

DYNLT4 p.Arg117Pro (c.350G>C) is very rare (popmax 0.000178%, nfe) (gnomAD).

What do computational predictors say about DYNLT4 p.Arg117Pro (c.350G>C)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

DYNLT4 p.Arg117Pro

c.350G>C · VCV4245906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000178%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -11.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP 0.63, phastCons 0.31
Regional constraint	o/e 1.01	unconstrained · MANE · 662 bp · p 0.79 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000178% European (non-Finnish) · 2/1,125,162 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000135% 2/1,485,500 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: DYNLT4
Protein: p.Arg117Pro
Coding: c.350G>C
MANE Select: NM_001377534
Type: single nucleotide variant
Location: chr1:44806319 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.02

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

Similar variants

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
DYNLT4 p.Arg102His 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-arg117pro (accessed [today's date]).

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