Is ERMN p.Ala93Pro (c.277G>C) pathogenic?

ERMN p.Ala93Pro (c.277G>C) is classified Uncertain significance in ERMN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.8107); Very rare (popmax 0.00167%, amr).

How common is ERMN p.Ala93Pro (c.277G>C) in the general population?

ERMN p.Ala93Pro (c.277G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ERMN p.Ala93Pro (c.277G>C)?

AlphaMissense predicts likely pathogenic (score 0.8107) — an in-silico prediction, not a clinical call.

ERMN p.Ala93Pro

c.277G>C · VCV3510208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8107	likely pathogenic · top 8% in ERMN
REVEL	0.339	indeterminate
SaProt	LLR -12.55	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 3.3	GERP 2.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,368 bp · p 0.37 · regional, not allelic
Overall
CADD	22.1	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 0.00167% Admixed American · 1/59,890 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00112% 18/1,612,632 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,890
Remaining individualsnot grpmax-eligible	0.0016%	62,420
European (non-Finnish)	0.00136%	73,713

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.Ala93Pro
Coding: c.277G>C
MANE Select: NM_020711
Type: single nucleotide variant
Location: chr2:157324727 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.95

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.Ala11Asp 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-ala93pro (accessed [today's date]).

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