Is ERMP1 p.Cys43Phe (c.128G>T) pathogenic?

ERMP1 p.Cys43Phe (c.128G>T) is classified Uncertain significance in ERMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.0777); Very rare (popmax 0.00146%, nfe).

How common is ERMP1 p.Cys43Phe (c.128G>T) in the general population?

ERMP1 p.Cys43Phe (c.128G>T) is very rare (popmax 0.00146%, nfe) (gnomAD).

What do computational predictors say about ERMP1 p.Cys43Phe (c.128G>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

ERMP1 p.Cys43Phe

c.128G>T · VCV3510220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00146%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -7.18	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 1.3	GERP 0.036, phastCons 0.004
Regional constraint	o/e 1.20	unconstrained · MANE · 46 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	12.22	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 0.00146% European (non-Finnish) · 17/1,162,272 alleles

Filtering AF 0.000891% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000728%

Overall 0.00128% 18/1,404,926 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00146%	68,369
South Asian	0.00117%	85,336

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.Cys43Phe
Coding: c.128G>T
MANE Select: NM_024896
Type: single nucleotide variant
Location: chr9:5832900 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.45
Residue 43: the 'disordered' region

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

Similar variants

ERMP1 p.Cys43Trp Uncertain significance ★ same residue
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

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-cys43phe (accessed [today's date]).

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