Is DYNLRB2 p.Arg58His (c.173G>A) pathogenic?

DYNLRB2 p.Arg58His (c.173G>A) is classified Uncertain significance in DYNLRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: ambiguous (0.3898); Ultra-rare (popmax 0.016%, afr).

How common is DYNLRB2 p.Arg58His (c.173G>A) in the general population?

DYNLRB2 p.Arg58His (c.173G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about DYNLRB2 p.Arg58His (c.173G>A)?

AlphaMissense predicts ambiguous (score 0.3898) — an in-silico prediction, not a clinical call.

DYNLRB2 p.Arg58His

c.173G>A · rs374443847 · VCV2223941

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3898 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Computational evidence

Protein change
AlphaMissense	0.3898	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -12.28	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 9,478 bp · p 0.025 · regional, not allelic
Overall
CADD	24.6	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 0.016% African / African-American · 12/74,902 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00385% 62/1,612,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,242
South Asian	0.0088%	11,363
Remaining individualsnot grpmax-eligible	0.00802%	12,474
East Asian	0.00669%	14,949
Admixed American	0.00333%	29,993
European (non-Finnish)	0.00271%	36,844

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: DYNLRB2
Protein: p.Arg58His
Coding: c.173G>A
MANE Select: NM_130897
dbSNP: rs374443847
Type: single nucleotide variant
Location: chr16:80549577 (GRCh38)
Gene constraint: LOEUF 1.624 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.08 · 1 PDB

Full DYNLRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLRB2 p.Arg58Cys Uncertain significance ★ ⚠ same residue
DYNLRB2 p.Leu66= Benign ★★ same type
DYNLRB2 p.Arg10Lys Uncertain significance ★ ⚠ same type
DYNLRB2 p.Asn36Thr Uncertain significance ★ ⚠ same type
DYNLRB2 p.Asn64Lys Uncertain significance ★ ⚠ same type
DYNLRB2 p.Asn93Ile Uncertain significance ★ ⚠ same type
DYNLRB2 p.Asp83Gly Uncertain significance ★ ⚠ same type
DYNLRB2 p.Glu3Asp 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/dynlrb2-p-arg58his (accessed [today's date]).

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