Is EPS8L2 p.Arg102Trp (c.304C>T) pathogenic?

EPS8L2 p.Arg102Trp (c.304C>T) is classified Uncertain significance in EPS8L2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: likely benign (0.2011); Ultra-rare (popmax 0.0142%, nfe).

How common is EPS8L2 p.Arg102Trp (c.304C>T) in the general population?

EPS8L2 p.Arg102Trp (c.304C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

What do computational predictors say about EPS8L2 p.Arg102Trp (c.304C>T)?

AlphaMissense predicts likely benign (score 0.2011) — an in-silico prediction, not a clinical call.

EPS8L2 p.Arg102Trp

c.304C>T · rs150769913 · VCV2601089

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2011 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2011	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -12.90	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.57	GERP -3.4, phastCons 0.017
Regional constraint	o/e 1.19	unconstrained · MANE · 18 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	24.8	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 0.0142% European (non-Finnish) · 167/1,179,924 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0112% 180/1,612,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,246
European (non-Finnish)grpmax	0.0142%	7,065
East Asian	0.00223%	44,878
African / African-American	0.00133%	74,926
South Asian	0.0011%	91,088

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EPS8L2
Protein: p.Arg102Trp
Coding: c.304C>T
MANE Select: NM_022772
dbSNP: rs150769913
Type: single nucleotide variant
Location: chr11:720200 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 2 PDB
Residue 102: the pid domain

Full EPS8L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8L2 p.Arg102Gly Uncertain significance ★ ⚠ same residue
EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
EPS8L2 p.Arg193Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg245Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg272Trp Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg365Cys Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg506Leu Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg76Trp 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/eps8l2-p-arg102trp (accessed [today's date]).

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