Is EAPP p.Arg236Lys (c.707G>A) pathogenic?

EAPP p.Arg236Lys (c.707G>A) is classified Uncertain significance in EAPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.0646); Very rare (popmax 0.00446%, eas).

How common is EAPP p.Arg236Lys (c.707G>A) in the general population?

EAPP p.Arg236Lys (c.707G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about EAPP p.Arg236Lys (c.707G>A)?

AlphaMissense predicts likely benign (score 0.0646) — an in-silico prediction, not a clinical call.

EAPP p.Arg236Lys

c.707G>A · rs762172753 · VCV2548763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0646	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -4.92	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 -2	GERP -3.9
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.76 · regional, not allelic
Overall
CADD	1.782	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

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000274% 4/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
European (non-Finnish)	0.000169%	590,019

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.Arg236Lys
Coding: c.707G>A
MANE Select: NM_018453
dbSNP: rs762172753
Type: single nucleotide variant
Location: chr14:34516461 (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.Arg236Ser Uncertain significance ★ ⚠ same residue
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

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-arg236lys (accessed [today's date]).

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