Is ASPA p.Arg71Cys (c.211C>T) pathogenic?

ASPA p.Arg71Cys (c.211C>T) is classified Conflicting classifications of pathogenicity in ASPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-20). AlphaMissense: likely pathogenic (0.8504); Very rare (popmax 0.00223%, eas); Associated with Canavan disease.

What condition is associated with ASPA p.Arg71Cys (c.211C>T)?

ASPA p.Arg71Cys (c.211C>T) is associated with Canavan disease (ClinVar).

How common is ASPA p.Arg71Cys (c.211C>T) in the general population?

ASPA p.Arg71Cys (c.211C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Canavan disease inherited?

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

What do computational predictors say about ASPA p.Arg71Cys (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.8504) — an in-silico prediction, not a clinical call.

ASPA p.Arg71Cys

c.211C>T · rs1192320601 · VCV1503500

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Canavan disease

Computational evidence

Protein change
AlphaMissense	0.8504	likely pathogenic
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -13.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.0073 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 6.2e-05% 1/1,614,034 alleles · very rare exomes 1/1,461,788 · genomes 0/152,246 · 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: ASPA
Protein: p.Arg71Cys
Coding: c.211C>T
MANE Select: NM_000049
dbSNP: rs1192320601
Type: single nucleotide variant
Location: chr17:3476370 (GRCh38)
Gene constraint: LOEUF 1.098 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.14 · 8 PDB
Residue 71: a binding site; an α-helix

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

Disease context

Canavan disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Canavan disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ASPA p.Arg71His Pathogenic/Likely pathogenic ★★ same residue
ASPA p.Arg71Leu Likely pathogenic ★ same residue
ASPA p.Arg71= Likely benign ★ same residue
ASPA c.236+2T>C Likely pathogenic ★★ same condition
ASPA c.237-1G>T Likely pathogenic ★★ same condition
ASPA c.237-2A>T Pathogenic/Likely pathogenic ★★ same condition
ASPA c.527-1G>A Likely pathogenic ★★ same condition
ASPA c.527-2A>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/aspa-p-arg71cys (accessed [today's date]).

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