Is ERP44 p.Arg285Trp (c.853C>T) pathogenic?

ERP44 p.Arg285Trp (c.853C>T) is classified Uncertain significance in ERP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.475); Very rare (popmax 0.000267%, nfe).

How common is ERP44 p.Arg285Trp (c.853C>T) in the general population?

ERP44 p.Arg285Trp (c.853C>T) is very rare (popmax 0.000267%, nfe) (gnomAD).

What do computational predictors say about ERP44 p.Arg285Trp (c.853C>T)?

AlphaMissense predicts ambiguous (score 0.475) — an in-silico prediction, not a clinical call.

ERP44 p.Arg285Trp

c.853C>T · VCV4019666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000267%, nfe)

Computational evidence

Protein change
AlphaMissense	0.475	ambiguous
REVEL	0.454	indeterminate
SaProt	LLR -11.51	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 25 kb · p 5.8e-06 · regional, not allelic
Overall
CADD	34.0	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 0.000267% European (non-Finnish) · 3/1,124,476 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000286% 4/1,400,782 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,944
European (non-Finnish)grpmax	0.000267%	374,825

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ERP44
Protein: p.Arg285Trp
Coding: c.853C>T
MANE Select: NM_015051
Type: single nucleotide variant
Location: chr9:100007599 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.07 · 5 PDB
Residue 285: the 'interaction with itpr1' region; an α-helix

Full ERP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERP44 p.Ala194Ser Uncertain significance ★ ⚠ same type
ERP44 p.Ala370Thr Uncertain significance ★ ⚠ same type
ERP44 p.Arg158Leu Uncertain significance ★ ⚠ same type
ERP44 p.Arg180Gln Uncertain significance ★ ⚠ same type
ERP44 p.Arg403Gln Uncertain significance ★ ⚠ same type
ERP44 p.Arg59Gly Uncertain significance ★ ⚠ same type
ERP44 p.Asn162Tyr Uncertain significance ★ ⚠ same type
ERP44 p.Asn208His 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/erp44-p-arg285trp (accessed [today's date]).

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