Is CA8 c.513+53C>A pathogenic?

CA8 c.513+53C>A is classified Benign in CA8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-19). Common (popmax 36.7%, afr) — too common for a highly-penetrant pathogenic allele.

CA8 c.513+53C>A

Q: How common is CA8 c.513+53C>A in the general population?

CA8 c.513+53C>A is common (popmax 36.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs73683396 · VCV1267451

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 36.7%, afr) — 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 +53	deep intronic (+53 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -3.5
Non-coding constraint	Z 0.45	1 kb window · o/e 0.96 · regional · uncalibrated
Overall
CADD	3.388	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.7% African / African-American · 25,747/70,106 alleles

Filtering AF 36.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.2%

Overall 27.8% 379,414/1,366,382 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	40.6%	2
African / African-Americangrpmax	36.7%	3
Amishnot grpmax-eligible	35.6%	3
Middle Eastern	33.3%	3
Remaining individualsnot grpmax-eligible	29.4%	3
European (non-Finnish)	27.5%	4
East Asian	27.2%	4
Admixed American	26.5%	4
South Asian	23.6%	4
Finnishnot grpmax-eligible	21.8%	5

Ashkenazi Jewish 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: CA8
Coding: c.513+53C>A
MANE Select: NM_004056
dbSNP: rs73683396
Type: single nucleotide variant
Location: chr8:60232231 (GRCh38)
Gene constraint: LOEUF 0.698 · pLI 0.24 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 1 PDB

Full CA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA8 p.Arg213Trp Uncertain significance ★★ ⚠ same type
CA8 p.Pro14Arg Uncertain significance ★★ ⚠ same type
CA8 p.Ser71Phe Uncertain significance ★★ ⚠ same type
CA8 c.100+154T>C Benign ★★ same type
CA8 c.100+19G>A Benign ★★ same type
CA8 c.100+37G>A Benign ★★ same type
CA8 c.100+81C>T Benign ★★ same type
CA8 c.100+85T>C Benign ★★ same type

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/ca8-c-513-plus-53c-a (accessed [today's date]).

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