Is DYNLT4 p.Val186Ala (c.557T>C) pathogenic?

DYNLT4 p.Val186Ala (c.557T>C) is classified Uncertain significance in DYNLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-25). AlphaMissense: likely benign (0.2968); Rare (popmax 0.364%, mid).

How common is DYNLT4 p.Val186Ala (c.557T>C) in the general population?

DYNLT4 p.Val186Ala (c.557T>C) is rare (popmax 0.364%, mid) (gnomAD).

What do computational predictors say about DYNLT4 p.Val186Ala (c.557T>C)?

AlphaMissense predicts likely benign (score 0.2968) — an in-silico prediction, not a clinical call.

DYNLT4 p.Val186Ala

c.557T>C · rs199603970 · VCV3086580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2968 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.364%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2968	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -6.90	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 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 662 bp · p 0.79 · regional, not allelic
Overall
CADD	22.7	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 0.364% Middle Eastern · 22/6,052 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.208%

Overall 0.00317% 51/1,607,756 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.364%	275
Remaining individualsnot grpmax-eligible	0.0193%	5,180
African / African-American	0.00133%	74,948
European (non-Finnish)	0.00127%	78,518
South Asian	0.00111%	90,408

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: DYNLT4
Protein: p.Val186Ala
Coding: c.557T>C
MANE Select: NM_001377534
dbSNP: rs199603970
Type: single nucleotide variant
Location: chr1:44806112 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.02

Full DYNLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNLT4 p.Val186Met Uncertain significance ★ ⚠ same residue
DYNLT4 p.Ala130Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala146Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala195Val Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala41Ser Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala58Thr Uncertain significance ★ ⚠ same type
DYNLT4 p.Ala72Thr 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/dynlt4-p-val186ala (accessed [today's date]).

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