Is ELAC2 p.Ala792Val (c.2375C>T) pathogenic?

ELAC2 p.Ala792Val (c.2375C>T) is classified Uncertain significance in ELAC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-21). AlphaMissense: likely benign (0.1124); Ultra-rare (popmax 0.0481%, afr); Associated with prostate cancer, hereditary, 2.

What condition is associated with ELAC2 p.Ala792Val (c.2375C>T)?

ELAC2 p.Ala792Val (c.2375C>T) is associated with prostate cancer, hereditary, 2, combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Ala792Val (c.2375C>T) in the general population?

ELAC2 p.Ala792Val (c.2375C>T) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ELAC2 p.Ala792Val (c.2375C>T)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ELAC2 p.Ala792Val

c.2375C>T · rs767378629 · VCV408862

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

prostate cancer, hereditary, 2

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -8.81	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	GERP -1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	16.43	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 0.0481% African / African-American · 36/74,894 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00857% 138/1,610,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,080
Admixed American	0.0167%	5,999
Remaining individualsnot grpmax-eligible	0.00801%	12,492
European (non-Finnish)	0.00712%	14,048
East Asian	0.00669%	14,958

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.Ala792Val
Coding: c.2375C>T
MANE Select: NM_018127
dbSNP: rs767378629
Type: single nucleotide variant
Location: chr17:12992924 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB

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

Disease context

prostate cancer, hereditary, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined oxidative phosphorylation defect type 17

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

ELAC2 p.Ala792= Likely benign ★★ same residue
ELAC2 p.Ala792Thr Uncertain significance ★ ⚠ same residue
ELAC2 p.Ala792_Leu794delinsVal 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

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-ala792val (accessed [today's date]).

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