Is DYNLT2 p.Asp114His (c.340G>C) pathogenic?

DYNLT2 p.Asp114His (c.340G>C) is classified Uncertain significance in DYNLT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.1885); Ultra-rare (popmax 0.0655%, amr).

How common is DYNLT2 p.Asp114His (c.340G>C) in the general population?

DYNLT2 p.Asp114His (c.340G>C) is ultra-rare (popmax 0.0655%, amr) (gnomAD).

What do computational predictors say about DYNLT2 p.Asp114His (c.340G>C)?

AlphaMissense predicts likely benign (score 0.1885) — an in-silico prediction, not a clinical call.

DYNLT2 p.Asp114His

c.340G>C · VCV4245892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0655%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1885	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.47	acceptor loss · deltas
Pangolin	Δ0.40	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 4.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 11 kb · p 0.45 · regional, not allelic
Overall
CADD	25.5	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 0.0655% Admixed American · 31/47,362 alleles

Filtering AF 0.0473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.0021% 31/1,475,608 alleles · ultra-rare

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.Asp114His
Coding: c.340G>C
MANE Select: NM_174910
Type: single nucleotide variant
Location: chr6:169743226 (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.Asp114Gly 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.Arg144Cys 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-asp114his (accessed [today's date]).

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