Is ERMAP p.Pro153Arg (c.458C>G) pathogenic?

ERMAP p.Pro153Arg (c.458C>G) is classified Uncertain significance in ERMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.1207); Very rare (popmax 0.000273%, nfe).

How common is ERMAP p.Pro153Arg (c.458C>G) in the general population?

ERMAP p.Pro153Arg (c.458C>G) is very rare (popmax 0.000273%, nfe) (gnomAD).

What do computational predictors say about ERMAP p.Pro153Arg (c.458C>G)?

AlphaMissense predicts likely benign (score 0.1207) — an in-silico prediction, not a clinical call.

ERMAP p.Pro153Arg

c.458C>G · VCV4019588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000273%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1207	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -7.21	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 2.7	GERP 0.69, phastCons 0.033
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.085 · regional, not allelic
Overall
CADD	16.33	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 0.000273% European (non-Finnish) · 3/1,098,608 alleles

Filtering AF 7.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000219% 3/1,372,714 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: ERMAP
Protein: p.Pro153Arg
Coding: c.458C>G
MANE Select: NM_001017922
Type: single nucleotide variant
Location: chr1:42835062 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22
Residue 153: a UniProt-annotated variant site (in sc-3 allele)

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

Similar variants

ERMAP p.Ala4Val Benign ★★ same type
ERMAP p.Arg73= Benign ★★ same type
ERMAP p.Ala157Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala34Ser Uncertain significance ★ ⚠ same type
ERMAP p.Ala449Ser Uncertain significance ★ ⚠ same type
ERMAP p.Arg117His Uncertain significance ★ ⚠ same type
ERMAP p.Arg231Gly Uncertain significance ★ ⚠ same type
ERMAP p.Arg234Gln 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/ermap-p-pro153arg (accessed [today's date]).

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