Is ERMP1 p.Arg415Cys (c.1243C>T) pathogenic?

ERMP1 p.Arg415Cys (c.1243C>T) is classified Uncertain significance in ERMP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-30). AlphaMissense: likely benign (0.2063); Rare (popmax 0.123%, eas).

How common is ERMP1 p.Arg415Cys (c.1243C>T) in the general population?

ERMP1 p.Arg415Cys (c.1243C>T) is rare (popmax 0.123%, eas) (gnomAD).

What do computational predictors say about ERMP1 p.Arg415Cys (c.1243C>T)?

AlphaMissense predicts likely benign (score 0.2063) — an in-silico prediction, not a clinical call.

ERMP1 p.Arg415Cys

c.1243C>T · VCV3510211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2063 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2063	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 46 kb · p 1.4e-11 · regional, not allelic
Overall
CADD	31.0	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 0.123% East Asian · 55/44,872 alleles

Filtering AF 0.0967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0873%

Overall 0.00502% 81/1,613,980 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.123%	816
African / African-American	0.008%	12,496
South Asian	0.00439%	22,769
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.0011%	90,766

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.Arg415Cys
Coding: c.1243C>T
MANE Select: NM_024896
Type: single nucleotide variant
Location: chr9:5811195 (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-arg415cys (accessed [today's date]).

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