Is PLA2G6 p.Asp331= (c.993C>T) pathogenic?

PLA2G6 p.Asp331= (c.993C>T) is classified Likely benign in PLA2G6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). No allele count reported in gnomAD v4.1 (AN 1,556,844); Associated with neurodegeneration with brain iron accumulation 2A.

What condition is associated with PLA2G6 p.Asp331= (c.993C>T)?

PLA2G6 p.Asp331= (c.993C>T) is associated with neurodegeneration with brain iron accumulation 2A (ClinVar).

How common is PLA2G6 p.Asp331= (c.993C>T) in the general population?

PLA2G6 p.Asp331= (c.993C>T) is no allele count reported in gnomAD v4.1 (AN 1,556,844) (gnomAD).

How is Infantile neuroaxonal dystrophy inherited?

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

PLA2G6 p.Asp331=

c.993C>T · rs1350725250 · VCV2008891

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,556,844)

Conditions

neurodegeneration with brain iron accumulation 2A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.032	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.5, phastCons 1
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,556,844). 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: PLA2G6
Protein: p.Asp331=
Coding: c.993C>T
MANE Select: NM_003560
dbSNP: rs1350725250
Type: single nucleotide variant
Location: chr22:38132915 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.16

Full PLA2G6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodegeneration with brain iron accumulation 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile neuroaxonal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PLA2G6 p.Asp331Tyr Pathogenic ★★ ⚠ same residue
PLA2G6 p.Asp331Asn Uncertain significance ★★ ⚠ same residue
PLA2G6 c.1078-1G>A Likely pathogenic ★★ same condition
PLA2G6 c.1186+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLA2G6 c.1186+1G>T Pathogenic/Likely pathogenic ★★ same condition
PLA2G6 c.1187-1G>A Pathogenic/Likely pathogenic ★★ same condition
PLA2G6 c.1349-2A>G Pathogenic/Likely pathogenic ★★ same condition
PLA2G6 c.1427+1G>A 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/pla2g6-p-asp331 (accessed [today's date]).

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