Is ELAC2 p.Ser52Cys (c.155C>G) pathogenic?

ELAC2 p.Ser52Cys (c.155C>G) is classified Conflicting classifications of pathogenicity in ELAC2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0749); Rare (popmax 0.159%, eas); Associated with Inborn genetic diseases.

What condition is associated with ELAC2 p.Ser52Cys (c.155C>G)?

ELAC2 p.Ser52Cys (c.155C>G) is associated with Inborn genetic diseases, prostate cancer, hereditary, 2, combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Ser52Cys (c.155C>G) in the general population?

ELAC2 p.Ser52Cys (c.155C>G) is rare (popmax 0.159%, eas) (gnomAD).

What do computational predictors say about ELAC2 p.Ser52Cys (c.155C>G)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

ELAC2 p.Ser52Cys

c.155C>G · rs9895963 · VCV241271

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.159%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -9.71	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 3.5	GERP -1.3, phastCons 0.98
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	13.81	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 0.159% East Asian · 71/44,668 alleles

Filtering AF 0.129% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.118%

Overall 0.0344% 553/1,607,972 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.212%	471
East Asiangrpmax	0.159%	629
African / African-American	0.0853%	1,172
Middle Eastern	0.0499%	2,005
Admixed American	0.0421%	2,375
South Asian	0.0232%	4,303
European (non-Finnish)	0.0201%	4,970

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser52Cys
Coding: c.155C>G
MANE Select: NM_018127
dbSNP: rs9895963
Type: single nucleotide variant
Location: chr17:13017793 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 52: a UniProt-annotated variant site (in)

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: prostate cancer, hereditary, 2 combined oxidative phosphorylation defect type 17

Similar variants

ELAC2 p.Ser52Phe Likely benign ★★ same residue
ELAC2 p.Ser52Pro Uncertain significance ★ ⚠ same residue
ELAC2 p.Ser52Tyr Uncertain significance ★ ⚠ same residue
ELAC2 p.Ser52= Likely benign ★ 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

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-ser52cys (accessed [today's date]).

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