Is ERMN p.Ala11Asp (c.32C>A) pathogenic?

ERMN p.Ala11Asp (c.32C>A) is classified Uncertain significance in ERMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: likely benign (0.1345); Ultra-rare (popmax 0.0223%, eas).

How common is ERMN p.Ala11Asp (c.32C>A) in the general population?

ERMN p.Ala11Asp (c.32C>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about ERMN p.Ala11Asp (c.32C>A)?

AlphaMissense predicts likely benign (score 0.1345) — an in-silico prediction, not a clinical call.

ERMN p.Ala11Asp

c.32C>A · rs762746151 · VCV2471536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1345 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1345	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -5.97	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 1.6	GERP -2.3, phastCons 0.008
Regional constraint	o/e 1.05	unconstrained · MANE · 4,368 bp · p 0.37 · regional, not allelic
Overall
CADD	13.68	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 0.0223% East Asian · 10/44,902 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.000743% 12/1,614,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,032

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: ERMN
Protein: p.Ala11Asp
Coding: c.32C>A
MANE Select: NM_020711
dbSNP: rs762746151
Type: single nucleotide variant
Location: chr2:157325611 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.95
Residue 11: the 'disordered' region

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

Similar variants

ERMN p.Ala52Thr Benign ★★ same type
ERMN c.-27T>G Uncertain significance ★ same type
ERMN p.Ala93Pro Uncertain significance ★ ⚠ same type
ERMN p.Arg110Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg128Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg147Gly Uncertain significance ★ ⚠ same type
ERMN p.Arg163Leu Uncertain significance ★ ⚠ same type
ERMN p.Asn193Ile 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/ermn-p-ala11asp (accessed [today's date]).

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