Is ALS2CL p.Pro290= (c.870C>G) pathogenic?

ALS2CL p.Pro290= (c.870C>G) is classified Likely benign in ALS2CL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). Absent from gnomAD v4.1.

How common is ALS2CL p.Pro290= (c.870C>G) in the general population?

ALS2CL p.Pro290= (c.870C>G) is absent from gnomAD v4.1 (gnomAD).

ALS2CL p.Pro290=

c.870C>G · VCV4962097

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -11	GERP -2.8
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

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: ALS2CL
Protein: p.Pro290=
Coding: c.870C>G
MANE Select: NM_147129
Type: single nucleotide variant
Location: chr3:46683824 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.50

Full ALS2CL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALS2CL p.Ala207Ser Uncertain significance ★ ⚠ same type
ALS2CL p.Ala212Thr Uncertain significance ★ ⚠ same type
ALS2CL p.Ala343Thr Uncertain significance ★ ⚠ same type
ALS2CL p.Ala35Val Uncertain significance ★ ⚠ same type
ALS2CL p.Ala512Val Uncertain significance ★ ⚠ same type
ALS2CL p.Ala701Thr Uncertain significance ★ ⚠ same type
ALS2CL p.Ala713Thr Uncertain significance ★ ⚠ same type
ALS2CL p.Arg11Trp Uncertain significance ★ ⚠ same type

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/als2cl-p-pro290 (accessed [today's date]).

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