Is ERLIN1 p.Ala41= (c.123T>G) pathogenic?

ERLIN1 p.Ala41= (c.123T>G) is classified Likely benign in ERLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-02). Ultra-rare (popmax 0.0147%, afr); Associated with hereditary spastic paraplegia 62.

What condition is associated with ERLIN1 p.Ala41= (c.123T>G)?

ERLIN1 p.Ala41= (c.123T>G) is associated with hereditary spastic paraplegia 62 (ClinVar).

How common is ERLIN1 p.Ala41= (c.123T>G) in the general population?

ERLIN1 p.Ala41= (c.123T>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

How is Autosomal recessive spastic paraplegia type 62 inherited?

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

ERLIN1 p.Ala41=

c.123T>G · VCV4741854

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

hereditary spastic paraplegia 62

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -3.7, phastCons 1
Overall
CADD	8.959	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,870 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000744% 12/1,611,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,806
Admixed American	0.00167%	59,936

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: ERLIN1
Protein: p.Ala41=
Coding: c.123T>G
MANE Select: NM_006459
Type: single nucleotide variant
Location: chr10:100183828 (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-ala41 (accessed [today's date]).

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