Is ETFA p.Glu161Asp (c.483G>C) pathogenic?

ETFA p.Glu161Asp (c.483G>C) is classified Uncertain significance in ETFA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.1801); Very rare (popmax 0.00017%, nfe).

How common is ETFA p.Glu161Asp (c.483G>C) in the general population?

ETFA p.Glu161Asp (c.483G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ETFA p.Glu161Asp (c.483G>C)?

AlphaMissense predicts likely benign (score 0.1801) — an in-silico prediction, not a clinical call.

ETFA p.Glu161Asp

c.483G>C · rs1331535487 · VCV2500579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1801	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -3.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -3.7, phastCons 0.94
Regional constraint	o/e 0.86	unconstrained · MANE · 95 kb · p 0.0051 · regional, not allelic
Overall
CADD	12.41	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 0.00017% European (non-Finnish) · 2/1,179,088 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,784 alleles · very 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: ETFA
Protein: p.Glu161Asp
Coding: c.483G>C
MANE Select: NM_000126
dbSNP: rs1331535487
Type: single nucleotide variant
Location: chr15:76286450 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 161: the 'domain i' region

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

Similar variants

MADD p.Arg161His Benign ★★ ⚠ same residue
ETFA p.Glu161Lys Uncertain significance ★ ⚠ same residue
ETFA c.186+1G>A Likely pathogenic ★★ same type
ETFA c.39+1G>A Likely pathogenic ★★ same type
ETFA c.451+1G>A Likely pathogenic ★★ same type
ETFA c.452-2A>G Likely pathogenic ★★ same type
ETFA c.664+1G>A Likely pathogenic ★★ same type
ETFA c.665-1G>A Likely pathogenic ★★ 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/etfa-p-glu161asp (accessed [today's date]).

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