Is ALS2 p.His952fs (c.2845_2854dup) pathogenic?

ALS2 p.His952fs (c.28452854dup) is classified Pathogenic in ALS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-03). Absent from gnomAD.

How common is ALS2 p.His952fs (c.2845_2854dup) in the general population?

ALS2 p.His952fs (c.2845_2854dup) is absent from gnomAD (gnomAD).

ALS2 p.His952fs

c.2845_2854dup · rs1553506317 · VCV504060

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 34
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALS2
Protein: p.His952fs
Coding: c.2845_2854dup
MANE Select: NM_020919
dbSNP: rs1553506317
Type: Duplication
Location: chr2:201727762 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.69
Residue 952: the ph domain

Full ALS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALS2 p.His952Arg Uncertain significance ★★ ⚠ same residue
ALS2 p.His952= Likely benign ★★ same residue
ALS2 p.Tyr1017fs Likely pathogenic ★★ same type
ALS2 p.Val1525fs Pathogenic/Likely pathogenic ★★ same type
ALS2 p.Gly901fs Likely pathogenic ★ same type
ALS2 p.Ile1517fs Pathogenic ★ same type
ALS2 p.Leu723fs Likely pathogenic ★ same type
ALS2 p.Met903fs Pathogenic ★ 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/als2-p-his952fs (accessed [today's date]).

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