Is EPS8L2 p.Val7Met (c.19G>A) pathogenic?

EPS8L2 p.Val7Met (c.19G>A) is classified Conflicting classifications of pathogenicity in EPS8L2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.0718); Ultra-rare (popmax 0.0166%, mid).

How common is EPS8L2 p.Val7Met (c.19G>A) in the general population?

EPS8L2 p.Val7Met (c.19G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about EPS8L2 p.Val7Met (c.19G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

EPS8L2 p.Val7Met

c.19G>A · rs558489382 · VCV2070193

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.00	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 -0.47	GERP -2.1
Regional constraint	o/e 1.19	unconstrained · MANE · 18 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	3.234	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 0.0166% Middle Eastern · 1/6,024 alleles

Filtering AF 0.00614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00295% 47/1,594,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,024
East Asian	0.0115%	8,706
South Asian	0.0114%	8,782
Remaining individualsnot grpmax-eligible	0.00972%	10,292
African / African-American	0.00402%	24,849
European (non-Finnish)	0.00188%	53,262

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.Val7Met
Coding: c.19G>A
MANE Select: NM_022772
dbSNP: rs558489382
Type: single nucleotide variant
Location: chr11:709426 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 2 PDB

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

Similar variants

EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
EPS8L2 p.Arg102Trp Uncertain significance ★★ ⚠ 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-val7met (accessed [today's date]).

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