Is ASIC5 p.Pro490Ser (c.1468C>T) pathogenic?

ASIC5 p.Pro490Ser (c.1468C>T) is classified Uncertain significance in ASIC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: likely benign (0.0704); Absent from gnomAD v4.1.

How common is ASIC5 p.Pro490Ser (c.1468C>T) in the general population?

ASIC5 p.Pro490Ser (c.1468C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASIC5 p.Pro490Ser (c.1468C>T)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

ASIC5 p.Pro490Ser

c.1468C>T · VCV3436467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -5
Regional constraint	o/e 1.07	unconstrained · MANE · 36 kb · p 0.1 · regional, not allelic
Overall
CADD	3.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASIC5
Protein: p.Pro490Ser
Coding: c.1468C>T
MANE Select: NM_017419
Type: single nucleotide variant
Location: chr4:155829906 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.59 · 3 PDB

Full ASIC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC5 p.Ala218Gly Uncertain significance ★ ⚠ same type
ASIC5 p.Ala396Thr Uncertain significance ★ ⚠ same type
ASIC5 p.Ala435Val Uncertain significance ★ ⚠ same type
ASIC5 p.Arg284Cys Uncertain significance ★ ⚠ same type
ASIC5 p.Arg284His Uncertain significance ★ ⚠ same type
ASIC5 p.Arg34Gln Uncertain significance ★ ⚠ same type
ASIC5 p.Arg408Gly Uncertain significance ★ ⚠ same type
ASIC5 p.Arg408Trp 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/asic5-p-pro490ser (accessed [today's date]).

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