Is EPS8 p.Ser24= (c.72A>G) pathogenic?

EPS8 p.Ser24= (c.72A>G) is classified Likely benign in EPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0108%, amr).

How common is EPS8 p.Ser24= (c.72A>G) in the general population?

EPS8 p.Ser24= (c.72A>G) is ultra-rare (popmax 0.0108%, amr) (gnomAD).

EPS8 p.Ser24=

c.72A>G · rs778107195 · VCV1990188

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, amr)

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 -0.094	GERP -2.3, phastCons 0.7
Overall
CADD	7.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% Admixed American · 6/55,558 alleles

Filtering AF 0.00467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.000596% 9/1,509,310 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0108%	9,260
Remaining individualsnot grpmax-eligible	0.00344%	29,048
European (non-Finnish)	9.03e-05%	1,107,482

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: EPS8
Protein: p.Ser24=
Coding: c.72A>G
MANE Select: NM_004447
dbSNP: rs778107195
Type: single nucleotide variant
Location: chr12:15681290 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB
Residue 24: the 'disordered' region

Full EPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8 p.Ser24Leu Uncertain significance ★ same residue
EPS8 c.205-8A>G Uncertain significance ★★ same type
EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala219Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg432Gln 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/eps8-p-ser24 (accessed [today's date]).

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