Is DTNA p.Pro705Arg (c.2114C>G) pathogenic?

DTNA p.Pro705Arg (c.2114C>G) is classified Uncertain significance in DTNA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: ambiguous (0.3627); Absent from gnomAD v4.1; Associated with left ventricular noncompaction 1.

What condition is associated with DTNA p.Pro705Arg (c.2114C>G)?

DTNA p.Pro705Arg (c.2114C>G) is associated with left ventricular noncompaction 1 (ClinVar).

How common is DTNA p.Pro705Arg (c.2114C>G) in the general population?

DTNA p.Pro705Arg (c.2114C>G) is absent from gnomAD v4.1 (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DTNA p.Pro705Arg (c.2114C>G)?

AlphaMissense predicts ambiguous (score 0.3627) — an in-silico prediction, not a clinical call.

DTNA p.Pro705Arg

c.2114C>G · rs2522924028 · VCV2880248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3627 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

left ventricular noncompaction 1

Computational evidence

Protein change
AlphaMissense	0.3627	ambiguous
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.48, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,503 bp · p 0.81 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P678R vs ClinVar P705R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DTNA
Protein: p.Pro705Arg
Coding: c.2114C>G
MANE Select: NM_001386795
dbSNP: rs2522924028
Type: single nucleotide variant
Location: chr18:34879671 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB

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

Disease context

left ventricular noncompaction 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

DTNA c.1346+5G>C Uncertain significance ★★ same condition
DTNA c.362+1G>A Uncertain significance ★★ same condition
DTNA c.604-13T>G Uncertain significance ★★ same condition
DTNA p.Ala118Thr Uncertain significance ★★ ⚠ same condition
DTNA p.Ala232Val Uncertain significance ★★ ⚠ same condition
DTNA p.Ala302Thr Uncertain significance ★★ ⚠ same condition
DTNA p.Ala407Ser Uncertain significance ★★ ⚠ same condition
DTNA p.Ala430Val Uncertain significance ★★ ⚠ same condition

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/dtna-p-pro705arg (accessed [today's date]).

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