Is ELAC2 p.Ser52Phe (c.155C>T) pathogenic?

ELAC2 p.Ser52Phe (c.155C>T) is classified Likely benign in ELAC2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1009); Rare (popmax 0.72%, afr); Associated with combined oxidative phosphorylation defect type 17.

How common is ELAC2 p.Ser52Phe (c.155C>T) in the general population?

ELAC2 p.Ser52Phe (c.155C>T) is rare (popmax 0.72%, afr) (gnomAD).

What do computational predictors say about ELAC2 p.Ser52Phe (c.155C>T)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

ELAC2 p.Ser52Phe

Q: What condition is associated with ELAC2 p.Ser52Phe (c.155C>T)?

ELAC2 p.Ser52Phe (c.155C>T) is associated with combined oxidative phosphorylation defect type 17, prostate cancer, hereditary, 2 (ClinVar).

Q: How is Combined oxidative phosphorylation defect type 17 inherited?

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

c.155C>T · rs9895963 · VCV241272

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.72%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -9.34	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	10.67	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 0.72% African / African-American · 540/74,994 alleles

Filtering AF 0.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.65%

Overall 0.0542% 872/1,607,976 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.72%	139
Ashkenazi Jewishnot grpmax-eligible	0.238%	420
Remaining individualsnot grpmax-eligible	0.0788%	1,269
Middle Eastern	0.0499%	2,005
Admixed American	0.0455%	2,199
East Asian	0.0403%	2,482
South Asian	0.021%	4,756
European (non-Finnish)	0.0121%	8,238
Finnishnot grpmax-eligible	0.00484%	20,682

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.Ser52Phe
Coding: c.155C>T
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

combined oxidative phosphorylation defect type 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: prostate cancer, hereditary, 2

For Combined oxidative phosphorylation defect type 17 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ELAC2 p.Ser52Cys Conflicting classifications of pathogenicity ★ ⚠ 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-ser52phe (accessed [today's date]).

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