Is EAPP p.Ser211Cys (c.632C>G) pathogenic?

EAPP p.Ser211Cys (c.632C>G) is classified Uncertain significance in EAPP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.0789); Ultra-rare (popmax 0.056%, sas).

How common is EAPP p.Ser211Cys (c.632C>G) in the general population?

EAPP p.Ser211Cys (c.632C>G) is ultra-rare (popmax 0.056%, sas) (gnomAD).

What do computational predictors say about EAPP p.Ser211Cys (c.632C>G)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

EAPP p.Ser211Cys

c.632C>G · VCV3274330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -9.42	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 7.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.76 · regional, not allelic
Overall
CADD	21.4	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 0.056% South Asian · 51/91,064 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00409% 66/1,613,868 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0032%	31,251
East Asian	0.00223%	44,872
European (non-Finnish)	0.00102%	98,326

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.Ser211Cys
Coding: c.632C>G
MANE Select: NM_018453
Type: single nucleotide variant
Location: chr14:34516536 (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.Ser211Pro 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-ser211cys (accessed [today's date]).

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