Is EPS8L3 p.Pro344Ser (c.1030C>T) pathogenic?

EPS8L3 p.Pro344Ser (c.1030C>T) is classified Likely benign in EPS8L3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0826); Absent from gnomAD v4.1.

How common is EPS8L3 p.Pro344Ser (c.1030C>T) in the general population?

EPS8L3 p.Pro344Ser (c.1030C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPS8L3 p.Pro344Ser (c.1030C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

EPS8L3 p.Pro344Ser

c.1030C>T · VCV4250310

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.29	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 0.49	GERP 0.43, phastCons 0.96
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.6 · regional, not allelic
Overall
CADD	14.31	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPS8L3
Protein: p.Pro344Ser
Coding: c.1030C>T
MANE Select: NM_133181
Type: single nucleotide variant
Location: chr1:109757105 (GRCh38)
Gene constraint: LOEUF 1.052 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.46 · 1 PDB

Full EPS8L3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8L3 p.Leu453Pro Uncertain significance ★★ ⚠ same type
EPS8L3 p.Phe318Leu Uncertain significance ★★ ⚠ same type
EPS8L3 p.Thr36Ile Uncertain significance ★★ ⚠ same type
EPS8L3 p.Asp481= Benign ★★ same type
EPS8L3 p.Ala181Pro Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala215Thr Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala282Val Uncertain significance ★ ⚠ same type
EPS8L3 p.Ala8Thr 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/eps8l3-p-pro344ser (accessed [today's date]).

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