Is ERMP1 p.Pro742Ser (c.2224C>T) pathogenic?

ERMP1 p.Pro742Ser (c.2224C>T) is classified Uncertain significance in ERMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.801); Absent from gnomAD v4.1.

How common is ERMP1 p.Pro742Ser (c.2224C>T) in the general population?

ERMP1 p.Pro742Ser (c.2224C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERMP1 p.Pro742Ser (c.2224C>T)?

AlphaMissense predicts likely pathogenic (score 0.801) — an in-silico prediction, not a clinical call.

ERMP1 p.Pro742Ser

c.2224C>T · VCV4019605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.801 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.801	likely pathogenic
REVEL	0.429	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 46 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERMP1
Protein: p.Pro742Ser
Coding: c.2224C>T
MANE Select: NM_024896
Type: single nucleotide variant
Location: chr9:5798852 (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-pro742ser (accessed [today's date]).

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