Is IGFALS p.Gln482= (c.1446G>A) pathogenic?

IGFALS p.Gln482= (c.1446G>A) is classified Likely benign in IGFALS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-06). Very rare (popmax 6.26e-05%); Associated with IGFALS-related disorder.

What condition is associated with IGFALS p.Gln482= (c.1446G>A)?

IGFALS p.Gln482= (c.1446G>A) is associated with IGFALS-related disorder (ClinVar).

How common is IGFALS p.Gln482= (c.1446G>A) in the general population?

IGFALS p.Gln482= (c.1446G>A) is very rare (popmax 6.26e-05%) (gnomAD).

IGFALS p.Gln482=

c.1446G>A · rs2548155936 · VCV3053708

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.26e-05%)

Conditions

IGFALS-related disorder

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 0.24	GERP -3.2, phastCons 0.007
Overall
CADD	1.311	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.26e-05%

Overall 6.26e-05% 1/1,597,202 alleles · very rare exomes 1/1,444,868 · genomes 0/152,334 · joint denominator

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: IGFALS
Protein: p.Gln482=
Coding: c.1446G>A
MANE Select: NM_004970
dbSNP: rs2548155936
Type: single nucleotide variant
Location: chr16:1790972 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 91.13 · 1 PDB

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

Disease context

IGFALS-related disorder

Similar variants

IGFALS p.Gln482Ter Uncertain significance ★ same residue
IGFALS p.Leu134Gln Pathogenic ★ same condition
IGFALS p.Phe602Cys Likely pathogenic ★ same condition
IGFALS p.Asn492Ser Uncertain significance ★ same condition
IGFALS p.Pro73Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
IGFALS c.17-52C>T Benign same condition
IGFALS p.Asp51= Likely benign same condition
IGFALS p.Glu35fs Pathogenic/Likely pathogenic ★★ 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/igfals-p-gln482 (accessed [today's date]).

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