Is DYNLT2 p.Arg50Gly (c.148A>G) pathogenic?

DYNLT2 p.Arg50Gly (c.148A>G) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.1932); Ultra-rare (popmax 0.0483%, nfe).

How common is DYNLT2 p.Arg50Gly (c.148A>G) in the general population?

DYNLT2 p.Arg50Gly (c.148A>G) is ultra-rare (popmax 0.0483%, nfe) (gnomAD).

What do computational predictors say about DYNLT2 p.Arg50Gly (c.148A>G)?

AlphaMissense predicts likely benign (score 0.1932) — an in-silico prediction, not a clinical call.

DYNLT2 p.Arg50Gly

c.148A>G · rs148750299 · VCV2558990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1932 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1932	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP 3.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	19.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% European (non-Finnish) · 570/1,179,894 alleles

Filtering AF 0.045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0437%

Overall 0.0369% 595/1,613,508 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0224%	4,462
African / African-American	0.0107%	9,366
Admixed American	0.00167%	59,976
Finnishnot grpmax-eligible	0.00157%	63,736
South Asian	0.0011%	91,068

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: DYNLT2
Protein: p.Arg50Gly
Coding: c.148A>G
MANE Select: NM_174910
dbSNP: rs148750299
Type: single nucleotide variant
Location: chr6:169744247 (GRCh38)
Gene constraint: LOEUF 1.376 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.20

Full DYNLT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT2 p.Ala130Val Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala164Val Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala178Thr Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala68Thr Uncertain significance ★ ⚠ same type
DYNLT2 p.Ala84Ser Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg132Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144Cys Uncertain significance ★ ⚠ same type
DYNLT2 p.Arg144His 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/dynlt2-p-arg50gly (accessed [today's date]).

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