Is DYNLT2 p.Val187Met (c.559G>A) pathogenic?

DYNLT2 p.Val187Met (c.559G>A) is classified Likely benign in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.1816); Rare (popmax 0.427%, amr).

How common is DYNLT2 p.Val187Met (c.559G>A) in the general population?

DYNLT2 p.Val187Met (c.559G>A) is rare (popmax 0.427%, amr) (gnomAD).

What do computational predictors say about DYNLT2 p.Val187Met (c.559G>A)?

AlphaMissense predicts likely benign (score 0.1816) — an in-silico prediction, not a clinical call.

DYNLT2 p.Val187Met

c.559G>A · rs144598809 · VCV3086563

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1816 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.427%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1816	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.85	GERP -3.1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	9.909	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 0.427% Admixed American · 256/60,012 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.367%

Overall 0.019% 307/1,614,040 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.427%	234
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0128%	7,813
African / African-American	0.00933%	10,720
European (non-Finnish)	0.00271%	36,873
South Asian	0.0022%	45,535

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.Val187Met
Coding: c.559G>A
MANE Select: NM_174910
dbSNP: rs144598809
Type: single nucleotide variant
Location: chr6:169740223 (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-val187met (accessed [today's date]).

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