Is TMEM43 p.Phe161= (c.483C>T) pathogenic?

TMEM43 p.Phe161= (c.483C>T) is classified Likely benign in TMEM43 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0308%, sas); Associated with arrhythmogenic right ventricular dysplasia 5.

What condition is associated with TMEM43 p.Phe161= (c.483C>T)?

TMEM43 p.Phe161= (c.483C>T) is associated with arrhythmogenic right ventricular dysplasia 5, cardiomyopathy (ClinVar).

How common is TMEM43 p.Phe161= (c.483C>T) in the general population?

TMEM43 p.Phe161= (c.483C>T) is ultra-rare (popmax 0.0308%, sas) (gnomAD).

TMEM43 p.Phe161=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.483C>T · rs772842801 · VCV926361

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, sas)

Conditions

arrhythmogenic right ventricular dysplasia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -4.3	GERP -2.8
Overall
CADD	8.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0308% South Asian · 28/91,044 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00229% 37/1,613,916 alleles · ultra-rare exomes 36/1,461,718 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0308%	3,252
Admixed American	0.005%	20,002
African / African-American	0.00267%	37,458
European (non-Finnish)	0.000339%	294,991

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: TMEM43
Protein: p.Phe161=
Coding: c.483C>T
MANE Select: NM_024334
dbSNP: rs772842801
Type: single nucleotide variant
Location: chr3:14132906 (GRCh38)
Gene constraint: LOEUF 1.13 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 89.92

Full TMEM43 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

TMEM43 p.Phe161Cys Uncertain significance ★ ⚠ same residue
TMEM43 p.Phe161fs Uncertain significance ★★ same residue
TMEM43 p.Phe161Val Uncertain significance ★ ⚠ same residue
TMEM43 p.Ser358Leu Pathogenic ★★ ⚠ same condition
TMEM43 c.1000+2T>C Uncertain significance ★★ same condition
TMEM43 c.1000+5G>T Uncertain significance ★★ same condition
TMEM43 c.1000+6T>C Uncertain significance ★★ same condition
TMEM43 c.13-1G>C 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/tmem43-p-phe161 (accessed [today's date]).

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