Is DYNLRB2 p.Pro29Ser (c.85C>T) pathogenic?

DYNLRB2 p.Pro29Ser (c.85C>T) is classified Uncertain significance in DYNLRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.6562); Ultra-rare (popmax 0.021%, nfe).

How common is DYNLRB2 p.Pro29Ser (c.85C>T) in the general population?

DYNLRB2 p.Pro29Ser (c.85C>T) is ultra-rare (popmax 0.021%, nfe) (gnomAD).

What do computational predictors say about DYNLRB2 p.Pro29Ser (c.85C>T)?

AlphaMissense predicts likely pathogenic (score 0.6562) — an in-silico prediction, not a clinical call.

DYNLRB2 p.Pro29Ser

c.85C>T · rs143006037 · VCV3086556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6562 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.021%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6562	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -14.76	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.4, 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 0.021% European (non-Finnish) · 245/1,167,944 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.0159% 254/1,593,930 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.021%	4,767
Remaining individualsnot grpmax-eligible	0.0065%	15,393
African / African-American	0.00537%	18,620
East Asian	0.00224%	44,598

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.Pro29Ser
Coding: c.85C>T
MANE Select: NM_130897
dbSNP: rs143006037
Type: single nucleotide variant
Location: chr16:80549489 (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.Leu66= Benign ★★ same type
DYNLRB2 p.Arg10Lys Uncertain significance ★ ⚠ same type
DYNLRB2 p.Arg58Cys Uncertain significance ★ same type
DYNLRB2 p.Arg58His 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

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-pro29ser (accessed [today's date]).

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