Is EAPP p.Ala183Val (c.548C>T) pathogenic?

EAPP p.Ala183Val (c.548C>T) is classified Uncertain significance in EAPP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.9381); Very rare (popmax 8.48e-05%, nfe).

How common is EAPP p.Ala183Val (c.548C>T) in the general population?

EAPP p.Ala183Val (c.548C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about EAPP p.Ala183Val (c.548C>T)?

AlphaMissense predicts likely pathogenic (score 0.9381) — an in-silico prediction, not a clinical call.

EAPP p.Ala183Val

c.548C>T · VCV4015893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9381 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9381	likely pathogenic
REVEL	0.5	indeterminate
SaProt	LLR -12.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.76 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,604 alleles

Overall 0.000662% 1/150,988 alleles · very rare

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: EAPP
Protein: p.Ala183Val
Coding: c.548C>T
MANE Select: NM_018453
Type: single nucleotide variant
Location: chr14:34524730 (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.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
EAPP p.Arg236Ser 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-ala183val (accessed [today's date]).

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