Is ERLIN2 p.Ile295Thr (c.884T>C) pathogenic?

ERLIN2 p.Ile295Thr (c.884T>C) is classified Uncertain significance in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-03). AlphaMissense: likely pathogenic (0.966); Very rare (popmax 0.00533%, afr); Associated with Inborn genetic diseases.

What condition is associated with ERLIN2 p.Ile295Thr (c.884T>C)?

ERLIN2 p.Ile295Thr (c.884T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ERLIN2 p.Ile295Thr (c.884T>C) in the general population?

ERLIN2 p.Ile295Thr (c.884T>C) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about ERLIN2 p.Ile295Thr (c.884T>C)?

AlphaMissense predicts likely pathogenic (score 0.966) — an in-silico prediction, not a clinical call.

ERLIN2 p.Ile295Thr

c.884T>C · rs552965642 · VCV2231154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.966	likely pathogenic
REVEL	0.642	indeterminate
SaProt	LLR -12.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 9,452 bp · p 1e-10 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00533% African / African-American · 4/74,980 alleles

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

Overall 0.00031% 5/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,745
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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: ERLIN2
Protein: p.Ile295Thr
Coding: c.884T>C
MANE Select: NM_007175
dbSNP: rs552965642
Type: single nucleotide variant
Location: chr8:37753979 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB
Residue 295: the 'interaction with erlin1' region

Full ERLIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERLIN2 p.Ala288Pro Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Arg211Gln Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Asp300Gly Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Gly46Ser Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Ile26Leu Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Leu274Met Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Met83Ile Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Pro331Leu Uncertain significance ★★ ⚠ same condition

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/erlin2-p-ile295thr (accessed [today's date]).

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