Is ERLIN1 p.Val204Ile (c.610G>A) pathogenic?

ERLIN1 p.Val204Ile (c.610G>A) is classified Uncertain significance in ERLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-26). AlphaMissense: ambiguous (0.4067); Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 62.

What condition is associated with ERLIN1 p.Val204Ile (c.610G>A)?

ERLIN1 p.Val204Ile (c.610G>A) is associated with hereditary spastic paraplegia 62 (ClinVar).

How common is ERLIN1 p.Val204Ile (c.610G>A) in the general population?

ERLIN1 p.Val204Ile (c.610G>A) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive spastic paraplegia type 62 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ERLIN1 p.Val204Ile (c.610G>A)?

AlphaMissense predicts ambiguous (score 0.4067) — an in-silico prediction, not a clinical call.

ERLIN1 p.Val204Ile

c.610G>A · rs1589525631 · VCV639284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 62

Computational evidence

Protein change
AlphaMissense	0.4067	ambiguous
REVEL	0.55	indeterminate
SaProt	LLR -10.79	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 31 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	25.2	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

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: ERLIN1
Protein: p.Val204Ile
Coding: c.610G>A
MANE Select: NM_006459
dbSNP: rs1589525631
Type: single nucleotide variant
Location: chr10:100164049 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 4 PDB

Full ERLIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 62 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 62 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ERLIN1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala254Ser Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala258Val Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala292Ser Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Arg243His Uncertain significance ★★ ⚠ same condition
ERLIN1 p.His26Asp Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ile223Thr 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/erlin1-p-val204ile (accessed [today's date]).

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