Is ARSA p.Ala316Asp (c.947C>A) pathogenic?

ARSA p.Ala316Asp (c.947C>A) is classified Uncertain significance in ARSA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-06). Absent from gnomAD v4.1; Associated with autosomal recessive sideroblastic anemia.

What condition is associated with ARSA p.Ala316Asp (c.947C>A)?

ARSA p.Ala316Asp (c.947C>A) is associated with autosomal recessive sideroblastic anemia, metachromatic leukodystrophy (ClinVar).

How common is ARSA p.Ala316Asp (c.947C>A) in the general population?

ARSA p.Ala316Asp (c.947C>A) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive sideroblastic anemia inherited?

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

ARSA p.Ala316Asp

c.947C>A · rs1569078754 · VCV634567

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive sideroblastic anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.957	strongly pathogenic-leaning
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,631 bp · p 0.96 · regional, not allelic
Overall
CADD	34.0	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: ARSA
Protein: p.Ala316Asp
Coding: c.947C>A
MANE Select: NM_000487
dbSNP: rs1569078754
Type: single nucleotide variant
Location: chr22:50626186 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 10 PDB
Residue 316: a β-strand; a disulfide bond

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

Disease context

autosomal recessive sideroblastic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: metachromatic leukodystrophy

For Autosomal recessive sideroblastic anemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ARSA p.Ala316Thr Conflicting classifications of pathogenicity ★ same residue
ARSA c.1107+1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSA c.1107+1G>T Pathogenic ★★ same condition
ARSA c.1108-2A>G Pathogenic ★★ same condition
ARSA c.1108-3C>G Pathogenic/Likely pathogenic ★★ same condition
ARSA c.1210+1G>A Pathogenic ★★ same condition
ARSA c.224+1G>A Likely pathogenic ★★ same condition
ARSA c.225-1G>C 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/arsa-p-ala316asp (accessed [today's date]).

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