Is ERLIN2 p.Ala2Val (c.5C>T) pathogenic?

ERLIN2 p.Ala2Val (c.5C>T) is classified Uncertain significance in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.1955); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ERLIN2 p.Ala2Val (c.5C>T)?

ERLIN2 p.Ala2Val (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ERLIN2 p.Ala2Val (c.5C>T) in the general population?

ERLIN2 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERLIN2 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.1955) — an in-silico prediction, not a clinical call.

ERLIN2 p.Ala2Val

c.5C>T · VCV4250848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1955	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -7.22	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 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 6,689 bp · p 9.5e-05 · regional, not allelic
Overall
CADD	27.8	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

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: ERLIN2
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_007175
Type: single nucleotide variant
Location: chr8:37737927 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB

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-ala2val (accessed [today's date]).

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