Is ASIC3 p.Ala520= (c.1560C>T) pathogenic?

ASIC3 p.Ala520= (c.1560C>T) is classified Uncertain significance in ASIC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). Ultra-rare (popmax 0.0413%, afr).

How common is ASIC3 p.Ala520= (c.1560C>T) in the general population?

ASIC3 p.Ala520= (c.1560C>T) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

ASIC3 p.Ala520=

c.1560C>T · VCV4154763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.101	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 0.53, phastCons 1
Overall
CADD	5.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0413% African / African-American · 31/75,048 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00242% 39/1,614,196 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,421
Admixed American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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: ASIC3
Protein: p.Ala520=
Coding: c.1560C>T
MANE Select: NM_004769
Type: single nucleotide variant
Location: chr7:151052616 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.15

Full ASIC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC3 p.Ala520Thr Likely benign ★ same residue
ASIC3 p.Arg79Ter Uncertain significance ★★ same type
ASIC3 p.Pro289Ser Benign ★★ same type
ASIC3 c.1518-4G>A Uncertain significance ★ same type
ASIC3 c.*27C>T Uncertain significance ★ same type
ASIC3 c.*3C>A Uncertain significance ★ same type
ASIC3 c.*3C>T Uncertain significance ★ same type
ASIC3 p.Ala110Ser Uncertain significance ★ ⚠ 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/asic3-p-ala520 (accessed [today's date]).

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