Is EPS8L2 p.Pro308= (c.924C>T) pathogenic?

EPS8L2 p.Pro308= (c.924C>T) is classified Benign in EPS8L2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele.

EPS8L2 p.Pro308=

Q: How common is EPS8L2 p.Pro308= (c.924C>T) in the general population?

EPS8L2 p.Pro308= (c.924C>T) is common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.924C>T · rs7949926 · VCV1245774

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 24.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.46	GERP -2.9, phastCons 0.055
Overall
CADD	12.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.4% African / African-American · 18,130/74,446 alleles

Filtering AF 24.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.9%

Overall 9.41% 150,288/1,596,542 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24.4%	4
Finnishnot grpmax-eligible	10.5%	10
Amishnot grpmax-eligible	9.67%	10
Remaining individualsnot grpmax-eligible	9.53%	10
European (non-Finnish)	9.28%	11
Middle Eastern	7.59%	13
Ashkenazi Jewishnot grpmax-eligible	7.29%	14
Admixed American	5.3%	19
South Asian	4.61%	22
East Asian	2.82%	35

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.Pro308=
Coding: c.924C>T
MANE Select: NM_022772
dbSNP: rs7949926
Type: single nucleotide variant
Location: chr11:721931 (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.Pro308Ser Uncertain significance ⚠ same residue
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

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-pro308 (accessed [today's date]).

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