Is ELAC2 p.Arg104Cys (c.310C>T) pathogenic?

ELAC2 p.Arg104Cys (c.310C>T) is classified Uncertain significance in ELAC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-04). AlphaMissense: likely benign (0.1901); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with ELAC2 p.Arg104Cys (c.310C>T)?

ELAC2 p.Arg104Cys (c.310C>T) is associated with Inborn genetic diseases, combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Arg104Cys (c.310C>T) in the general population?

ELAC2 p.Arg104Cys (c.310C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ELAC2 p.Arg104Cys (c.310C>T)?

AlphaMissense predicts likely benign (score 0.1901) — an in-silico prediction, not a clinical call.

ELAC2 p.Arg104Cys

c.310C>T · rs748205884 · VCV1356617

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1901	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,864 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000682% 11/1,613,924 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,864
South Asian	0.0011%	91,076
European (non-Finnish)	0.000763%	131,113

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: ELAC2
Protein: p.Arg104Cys
Coding: c.310C>T
MANE Select: NM_018127
dbSNP: rs748205884
Type: single nucleotide variant
Location: chr17:13016919 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 104: an α-helix

Full ELAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined oxidative phosphorylation defect type 17

Similar variants

ELAC2 p.Arg104His Uncertain significance ★ ⚠ same residue
ELAC2 c.1080-1G>C Likely pathogenic ★★ same condition
ELAC2 c.1423+1G>A Pathogenic ★★ same condition
ELAC2 c.1908+1G>A Likely pathogenic ★★ same condition
ELAC2 c.245+2T>A Pathogenic/Likely pathogenic ★★ same condition
ELAC2 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same condition
ELAC2 p.Gln18Ter Pathogenic ★★ same condition
ELAC2 p.Glu30Ter Pathogenic/Likely pathogenic ★★ 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/elac2-p-arg104cys (accessed [today's date]).

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