Is EPX p.Pro292Leu (c.875C>T) pathogenic?

EPX p.Pro292Leu (c.875C>T) is classified Benign in EPX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-18). AlphaMissense: likely benign (0.0885); Low-frequency (popmax 4.54%, afr).

How common is EPX p.Pro292Leu (c.875C>T) in the general population?

EPX p.Pro292Leu (c.875C>T) is low-frequency (popmax 4.54%, afr) (gnomAD).

What do computational predictors say about EPX p.Pro292Leu (c.875C>T)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

EPX p.Pro292Leu

c.875C>T · rs33971258 · VCV770269

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.54%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -4.49	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 1.5	GERP 1.9, phastCons 0.002
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.44 · regional, not allelic
Overall
CADD	20.7	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 4.54% African / African-American · 3,401/74,976 alleles

Filtering AF 4.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.36%

Overall 0.253% 4,083/1,614,098 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.54%	22
Remaining individualsnot grpmax-eligible	0.432%	232
Admixed American	0.403%	248
Middle Eastern	0.231%	433
South Asian	0.0132%	7,590
European (non-Finnish)	0.0122%	8,195

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: EPX
Protein: p.Pro292Leu
Coding: c.875C>T
MANE Select: NM_000502
dbSNP: rs33971258
Type: single nucleotide variant
Location: chr17:58197012 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.40 · 1 PDB
Residue 292: a UniProt-annotated variant site (in)

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

Similar variants

EPX c.170+5A>G Likely benign ★★ same type
EPX c.464+8C>T Benign ★★ same type
EPX c.801+1G>A Likely benign ★★ same type
EPX p.Asn572Tyr Benign ★★ same type
EPX p.Cys257Ter Benign ★★ same type
EPX p.Leu624= Benign/Likely benign ★★ same type
EPX p.Phe308Leu Likely benign ★★ same type
EPX p.Val35Ile Benign ★★ ⚠ same type

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/epx-p-pro292leu (accessed [today's date]).

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