Is EPX p.Arg151Trp (c.451C>T) pathogenic?

EPX p.Arg151Trp (c.451C>T) is classified Uncertain significance in EPX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1257); Rare (popmax 0.135%, sas).

How common is EPX p.Arg151Trp (c.451C>T) in the general population?

EPX p.Arg151Trp (c.451C>T) is rare (popmax 0.135%, sas) (gnomAD).

What do computational predictors say about EPX p.Arg151Trp (c.451C>T)?

AlphaMissense predicts likely benign (score 0.1257) — an in-silico prediction, not a clinical call.

EPX p.Arg151Trp

c.451C>T · rs370404238 · VCV2205099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1257 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1257	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.78	GERP -4
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.44 · regional, not allelic
Overall
CADD	20.2	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 0.135% South Asian · 123/91,018 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0108% 174/1,611,150 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.135%	740
Middle Eastern	0.0337%	2,967
African / African-American	0.008%	12,501
Admixed American	0.005%	20,008
European (non-Finnish)	0.00323%	30,985
Remaining individualsnot grpmax-eligible	0.0032%	31,206

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.Arg151Trp
Coding: c.451C>T
MANE Select: NM_000502
dbSNP: rs370404238
Type: single nucleotide variant
Location: chr17:58193818 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.40 · 1 PDB
Residue 151: a disulfide bond

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

Similar variants

EPX p.Arg151Gln Uncertain significance ★ ⚠ same residue
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

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-arg151trp (accessed [today's date]).

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