Is ERMP1 p.Ser367Cys (c.1100C>G) pathogenic?

ERMP1 p.Ser367Cys (c.1100C>G) is classified Uncertain significance in ERMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: ambiguous (0.4332); Very rare (popmax 0.00538%, afr).

How common is ERMP1 p.Ser367Cys (c.1100C>G) in the general population?

ERMP1 p.Ser367Cys (c.1100C>G) is very rare (popmax 0.00538%, afr) (gnomAD).

What do computational predictors say about ERMP1 p.Ser367Cys (c.1100C>G)?

AlphaMissense predicts ambiguous (score 0.4332) — an in-silico prediction, not a clinical call.

ERMP1 p.Ser367Cys

c.1100C>G · VCV4250907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4332 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00538%, afr)

Computational evidence

Protein change
AlphaMissense	0.4332	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -10.95	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 46 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00538% African / African-American · 4/74,418 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000249% 4/1,603,716 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: ERMP1
Protein: p.Ser367Cys
Coding: c.1100C>G
MANE Select: NM_024896
Type: single nucleotide variant
Location: chr9:5812139 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.45

Full ERMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERMP1 c.1021+6T>C Likely benign ★★ same type
ERMP1 p.Gly809= Benign ★★ same type
ERMP1 p.Ser531= Benign ★★ same type
ERMP1 p.Val404= Benign ★★ same type
ERMP1 p.Ala109Gly Uncertain significance ★ ⚠ same type
ERMP1 p.Ala109Val Uncertain significance ★ ⚠ same type
ERMP1 p.Ala112Thr Uncertain significance ★ ⚠ same type
ERMP1 p.Ala196Asp 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/ermp1-p-ser367cys (accessed [today's date]).

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