Is EAPP p.Ser263Cys (c.788C>G) pathogenic?

EAPP p.Ser263Cys (c.788C>G) is classified Uncertain significance in EAPP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-14). AlphaMissense: likely benign (0.1396); Absent from gnomAD v4.1.

How common is EAPP p.Ser263Cys (c.788C>G) in the general population?

EAPP p.Ser263Cys (c.788C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EAPP p.Ser263Cys (c.788C>G)?

AlphaMissense predicts likely benign (score 0.1396) — an in-silico prediction, not a clinical call.

EAPP p.Ser263Cys

c.788C>G · rs746678806 · VCV2255421

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1396 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1396	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.76 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: EAPP
Protein: p.Ser263Cys
Coding: c.788C>G
MANE Select: NM_018453
dbSNP: rs746678806
Type: single nucleotide variant
Location: chr14:34516380 (GRCh38)
Gene constraint: LOEUF 1.441 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.38

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

Similar variants

EAPP p.Arg239Gln Benign ★★ same type
EAPP p.Ala183Val Uncertain significance ★ ⚠ same type
EAPP p.Ala267Val Uncertain significance ★ ⚠ same type
EAPP p.Ala282Thr Uncertain significance ★ ⚠ same type
EAPP p.Ala95Ser Uncertain significance ★ ⚠ same type
EAPP p.Arg156Ser Uncertain significance ★ ⚠ same type
EAPP p.Arg229Ser Uncertain significance ★ ⚠ same type
EAPP p.Arg236Lys 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/eapp-p-ser263cys (accessed [today's date]).

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