Is ASIC3 p.Arg79Ter (c.235C>T) pathogenic?

ASIC3 p.Arg79Ter (c.235C>T) is classified Uncertain significance in ASIC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-11). Rare (popmax 0.218%, nfe).

How common is ASIC3 p.Arg79Ter (c.235C>T) in the general population?

ASIC3 p.Arg79Ter (c.235C>T) is rare (popmax 0.218%, nfe) (gnomAD).

ASIC3 p.Arg79Ter

c.235C>T · rs144223292 · VCV1703060

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.218%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3.6, phastCons 0.77
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.218% European (non-Finnish) · 2,572/1,179,930 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.208%

Overall 0.165% 2,666/1,613,756 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.218%	459
Remaining individualsnot grpmax-eligible	0.0832%	1,201
African / African-American	0.0307%	3,257
Finnishnot grpmax-eligible	0.0204%	4,914
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,798
Admixed American	0.005%	20,001
East Asian	0.00223%	44,884

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.Arg79Ter
Coding: c.235C>T
MANE Select: NM_004769
dbSNP: rs144223292
Type: single nucleotide variant
Location: chr7:151049120 (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.Arg79Gln Uncertain significance ★ ⚠ same residue
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
ASIC3 p.Ala120Thr 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-arg79ter (accessed [today's date]).

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