Is DYNLRB2 p.Val22Ala (c.65T>C) pathogenic?

DYNLRB2 p.Val22Ala (c.65T>C) is classified Uncertain significance in DYNLRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely pathogenic (0.7222); Very rare (popmax 0.00891%, eas).

How common is DYNLRB2 p.Val22Ala (c.65T>C) in the general population?

DYNLRB2 p.Val22Ala (c.65T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DYNLRB2 p.Val22Ala (c.65T>C)?

AlphaMissense predicts likely pathogenic (score 0.7222) — an in-silico prediction, not a clinical call.

DYNLRB2 p.Val22Ala

c.65T>C · VCV3506119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7222	likely pathogenic
REVEL	0.479	indeterminate
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.6, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 9,478 bp · p 0.025 · regional, not allelic
Overall
CADD	27.4	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 0.00891% East Asian · 4/44,874 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000479% 7/1,461,644 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
South Asian	0.0011%	91,046
European (non-Finnish)	0.00017%	589,936

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.Val22Ala
Coding: c.65T>C
MANE Select: NM_130897
Type: single nucleotide variant
Location: chr16:80543337 (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-val22ala (accessed [today's date]).

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