Is ASPA p.Asn77Ser (c.230A>G) pathogenic?

ASPA p.Asn77Ser (c.230A>G) is classified Conflicting classifications of pathogenicity in ASPA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-26). AlphaMissense: likely benign (0.1138); Rare (popmax 0.125%, sas); Associated with Inborn genetic diseases.

What condition is associated with ASPA p.Asn77Ser (c.230A>G)?

ASPA p.Asn77Ser (c.230A>G) is associated with Inborn genetic diseases, Canavan disease (ClinVar).

How common is ASPA p.Asn77Ser (c.230A>G) in the general population?

ASPA p.Asn77Ser (c.230A>G) is rare (popmax 0.125%, sas) (gnomAD).

What do computational predictors say about ASPA p.Asn77Ser (c.230A>G)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

ASPA p.Asn77Ser

c.230A>G · rs574328488 · VCV1134355

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.0073 · regional, not allelic
Overall
CADD	18.8	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 0.125% South Asian · 114/91,086 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0994%

Overall 0.00812% 131/1,613,852 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.125%	799
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.000509%	196,655

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.Asn77Ser
Coding: c.230A>G
MANE Select: NM_000049
dbSNP: rs574328488
Type: single nucleotide variant
Location: chr17:3476389 (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 77: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Canavan disease

Similar variants

ASPA p.Asn77fs Pathogenic ★ 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
ASPA c.527-2A>G Likely pathogenic ★★ same condition
ASPA c.634+1G>T 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/aspa-p-asn77ser (accessed [today's date]).

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