Is ELAC2 p.Arg112Gln (c.335G>A) pathogenic?

ELAC2 p.Arg112Gln (c.335G>A) is classified Uncertain significance in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.1823); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ELAC2 p.Arg112Gln (c.335G>A)?

ELAC2 p.Arg112Gln (c.335G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ELAC2 p.Arg112Gln (c.335G>A) in the general population?

ELAC2 p.Arg112Gln (c.335G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ELAC2 p.Arg112Gln (c.335G>A)?

AlphaMissense predicts likely benign (score 0.1823) — an in-silico prediction, not a clinical call.

ELAC2 p.Arg112Gln

c.335G>A · VCV4248046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1823	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	33.0	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 0.000169% European (non-Finnish) · 2/1,180,030 alleles

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

Overall 0.000137% 2/1,461,886 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: ELAC2
Protein: p.Arg112Gln
Coding: c.335G>A
MANE Select: NM_018127
Type: single nucleotide variant
Location: chr17:13016894 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 112: a β-strand

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

Similar variants

ELAC2 p.Glu482Ter Pathogenic/Likely pathogenic ★★ same condition
ELAC2 p.Ala344Thr Uncertain significance ★★ ⚠ same condition
ELAC2 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
ELAC2 p.Arg104Cys Uncertain significance ★★ ⚠ same condition
ELAC2 p.Arg166Gly Uncertain significance ★★ ⚠ same condition
ELAC2 p.Arg381His Uncertain significance ★★ ⚠ same condition
ELAC2 p.Arg404His Uncertain significance ★★ ⚠ same condition
ELAC2 p.Arg630Gln 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/elac2-p-arg112gln (accessed [today's date]).

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