Is DYNLT2 p.Arg144His (c.431G>A) pathogenic?

DYNLT2 p.Arg144His (c.431G>A) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely pathogenic (0.6323); Rare (popmax 0.101%, mid).

How common is DYNLT2 p.Arg144His (c.431G>A) in the general population?

DYNLT2 p.Arg144His (c.431G>A) is rare (popmax 0.101%, mid) (gnomAD).

What do computational predictors say about DYNLT2 p.Arg144His (c.431G>A)?

AlphaMissense predicts likely pathogenic (score 0.6323) — an in-silico prediction, not a clinical call.

DYNLT2 p.Arg144His

c.431G>A · VCV3274210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6323 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6323	likely pathogenic
REVEL	0.483	indeterminate
SaProt	LLR -10.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.101% Middle Eastern · 6/5,916 alleles

Filtering AF 0.0441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0301%

Overall 0.00481% 76/1,579,692 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.101%	986
Finnishnot grpmax-eligible	0.0223%	4,478
African / African-American	0.00941%	10,631
Remaining individualsnot grpmax-eligible	0.00496%	20,172
European (non-Finnish)	0.00363%	27,563
Admixed American	0.00341%	29,348
East Asian	0.00225%	44,358
South Asian	0.00116%	85,948

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.Arg144His
Coding: c.431G>A
MANE Select: NM_174910
Type: single nucleotide variant
Location: chr6:169743135 (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.Arg144Cys Uncertain significance ★ ⚠ same residue
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.Arg28Gly 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-arg144his (accessed [today's date]).

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