Is PLA2G6 p.Phe372= (c.1116C>T) pathogenic?

PLA2G6 p.Phe372= (c.1116C>T) is classified Likely benign in PLA2G6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-23). Ultra-rare (popmax 0.0933%, amr); Associated with neurodegeneration with brain iron accumulation 2A.

What condition is associated with PLA2G6 p.Phe372= (c.1116C>T)?

PLA2G6 p.Phe372= (c.1116C>T) is associated with neurodegeneration with brain iron accumulation 2A (ClinVar).

How common is PLA2G6 p.Phe372= (c.1116C>T) in the general population?

PLA2G6 p.Phe372= (c.1116C>T) is ultra-rare (popmax 0.0933%, amr) (gnomAD).

How is Infantile neuroaxonal dystrophy inherited?

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

PLA2G6 p.Phe372=

c.1116C>T · rs538112875 · VCV767210

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0933%, amr)

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	0.157	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	GERP -1.8, phastCons 0.96
Overall
CADD	12.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0933% Admixed American · 56/60,024 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.00458% 74/1,614,028 alleles · ultra-rare exomes 69/1,461,712 · genomes 5/152,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0933%	1,072
South Asian	0.00769%	13,011
African / African-American	0.004%	25,011
European (non-Finnish)	0.000678%	147,487

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: PLA2G6
Protein: p.Phe372=
Coding: c.1116C>T
MANE Select: NM_003560
dbSNP: rs538112875
Type: single nucleotide variant
Location: chr22:38129524 (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 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
PLA2G6 c.1592-2A>C Pathogenic/Likely pathogenic ★★ same condition
PLA2G6 c.1743-2A>G 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-phe372 (accessed [today's date]).

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