Is ERLIN2 p.Tyr59= (c.177T>C) pathogenic?

ERLIN2 p.Tyr59= (c.177T>C) is classified Likely benign in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). Ultra-rare (popmax 0.0347%, afr); Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Tyr59= (c.177T>C)?

ERLIN2 p.Tyr59= (c.177T>C) is associated with Spastic paraplegia (ClinVar).

How common is ERLIN2 p.Tyr59= (c.177T>C) in the general population?

ERLIN2 p.Tyr59= (c.177T>C) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

ERLIN2 p.Tyr59=

c.177T>C · rs376522883 · VCV2731837

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.17	GERP -3.9, phastCons 0.99
Overall
CADD	7.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/74,860 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00167% 27/1,612,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,879
Remaining individualsnot grpmax-eligible	0.0016%	62,418

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.Tyr59=
Coding: c.177T>C
MANE Select: NM_007175
dbSNP: rs376522883
Type: single nucleotide variant
Location: chr8:37740434 (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

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERLIN2 p.Ala151Val Pathogenic/Likely pathogenic ★★ same condition
ERLIN2 c.298+5G>A Uncertain significance ★★ same condition
ERLIN2 c.819+3A>G Uncertain significance ★★ same condition
ERLIN2 p.Ala290Val Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Ala99Thr Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Asn93Asp Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Gln154Pro Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Gln63Arg 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-tyr59 (accessed [today's date]).

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