Is EPHX3 p.Pro98= (c.294C>G) pathogenic?

EPHX3 p.Pro98= (c.294C>G) is classified Benign in EPHX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-01). Rare (popmax 0.786%, sas).

How common is EPHX3 p.Pro98= (c.294C>G) in the general population?

EPHX3 p.Pro98= (c.294C>G) is rare (popmax 0.786%, sas) (gnomAD).

EPHX3 p.Pro98=

c.294C>G · rs200237647 · VCV744463

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.786%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.063	GERP -2.4, phastCons 0.07
Overall
CADD	9.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.786% South Asian · 716/91,080 alleles

Filtering AF 0.738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.719%

Overall 0.0469% 757/1,613,964 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.786%	127
Remaining individualsnot grpmax-eligible	0.056%	1,786
East Asian	0.00446%	22,438
African / African-American	0.00266%	37,530
European (non-Finnish)	0.000169%	590,012

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: EPHX3
Protein: p.Pro98=
Coding: c.294C>G
MANE Select: NM_024794
dbSNP: rs200237647
Type: single nucleotide variant
Location: chr19:15231811 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.38

Full EPHX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHX3 p.Ala176Asp Uncertain significance ★ ⚠ same type
EPHX3 p.Ala176Thr Uncertain significance ★ ⚠ same type
EPHX3 p.Ala22Ser Uncertain significance ★ ⚠ same type
EPHX3 p.Ala65Ser Uncertain significance ★ ⚠ same type
EPHX3 p.Ala65Thr Uncertain significance ★ ⚠ same type
EPHX3 p.Arg114Cys Uncertain significance ★ ⚠ same type
EPHX3 p.Arg114His Uncertain significance ★ ⚠ same type
EPHX3 p.Arg118Gln Uncertain significance ★ ⚠ 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/ephx3-p-pro98 (accessed [today's date]).

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