Is ASPA c.634+302A>C pathogenic?

ASPA c.634+302A>C is classified Benign in ASPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). Common (popmax 55.1%, nfe) — too common for a highly-penetrant pathogenic allele.

ASPA c.634+302A>C

Q: How common is ASPA c.634+302A>C in the general population?

ASPA c.634+302A>C is common (popmax 55.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs12952852 · VCV1239539

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 55.1%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +302	deep intronic (+302 nt into the intron)
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP -0.24, phastCons 0.13
Non-coding constraint	Z 3.28	1 kb window · o/e 0.72 · regional · uncalibrated
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.1% European (non-Finnish) · 37,453/67,946 alleles

Filtering AF 54.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.5%

Overall 40.4% 61,471/152,082 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	62.2%	2
European (non-Finnish)grpmax	55.1%	2
Ashkenazi Jewishnot grpmax-eligible	47%	2
Finnishnot grpmax-eligible	46.3%	2
Remaining individualsnot grpmax-eligible	39.5%	3
Middle Eastern	36.4%	3
Admixed American	31.7%	3
African / African-American	24.5%	4
South Asian	19.4%	5
East Asian	0.656%	152

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.634+302A>C
MANE Select: NM_001170698 · reported on NM_000049
dbSNP: rs12952852
Type: single nucleotide variant
Location: chr17:3489644 (GRCh38)

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

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-c-634-plus-302a-c (accessed [today's date]).

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