Is DTNA p.Phe271= (c.813C>T) pathogenic?

DTNA p.Phe271= (c.813C>T) is classified Likely benign in DTNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). Very rare (popmax 0.00178%, nfe); Associated with left ventricular noncompaction 1.

What condition is associated with DTNA p.Phe271= (c.813C>T)?

DTNA p.Phe271= (c.813C>T) is associated with left ventricular noncompaction 1 (ClinVar).

How common is DTNA p.Phe271= (c.813C>T) in the general population?

DTNA p.Phe271= (c.813C>T) is very rare (popmax 0.00178%, nfe) (gnomAD).

How is Left ventricular noncompaction inherited?

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

DTNA p.Phe271=

c.813C>T · rs763237274 · VCV2128132

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

left ventricular noncompaction 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1, phastCons 1
Overall
CADD	13.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,962 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00151% 22/1,461,780 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,189
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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: DTNA
Protein: p.Phe271=
Coding: c.813C>T
MANE Select: NM_001386795
dbSNP: rs763237274
Type: single nucleotide variant
Location: chr18:34818267 (GRCh38)
Gene constraint: LOEUF 0.523 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 271: the 'interaction with magee1' region; an α-helix

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-phe271 (accessed [today's date]).

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