Is DYNLRB2 p.Glu85Lys (c.253G>A) pathogenic?

DYNLRB2 p.Glu85Lys (c.253G>A) is classified Uncertain significance in DYNLRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: ambiguous (0.5367); Very rare (popmax 0.00666%, amr).

How common is DYNLRB2 p.Glu85Lys (c.253G>A) in the general population?

DYNLRB2 p.Glu85Lys (c.253G>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about DYNLRB2 p.Glu85Lys (c.253G>A)?

AlphaMissense predicts ambiguous (score 0.5367) — an in-silico prediction, not a clinical call.

DYNLRB2 p.Glu85Lys

c.253G>A · rs189026572 · VCV2264715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5367	ambiguous
REVEL	0.134	moderately benign-leaning
SaProt	LLR -14.84	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 9,478 bp · p 0.025 · regional, not allelic
Overall
CADD	25.3	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 0.00666% Admixed American · 4/60,018 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000434% 7/1,614,078 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
South Asian	0.0011%	91,082
European (non-Finnish)	0.000169%	589,991

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.Glu85Lys
Coding: c.253G>A
MANE Select: NM_130897
dbSNP: rs189026572
Type: single nucleotide variant
Location: chr16:80550520 (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-glu85lys (accessed [today's date]).

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