Is ASIC2 p.Pro550Ser (c.1648C>T) pathogenic?

ASIC2 p.Pro550Ser (c.1648C>T) is classified Uncertain significance in ASIC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). AlphaMissense: ambiguous (0.3829); Very rare (popmax 0.00987%, nfe).

How common is ASIC2 p.Pro550Ser (c.1648C>T) in the general population?

ASIC2 p.Pro550Ser (c.1648C>T) is very rare (popmax 0.00987%, nfe) (gnomAD).

What do computational predictors say about ASIC2 p.Pro550Ser (c.1648C>T)?

AlphaMissense predicts ambiguous (score 0.3829) — an in-silico prediction, not a clinical call.

ASIC2 p.Pro550Ser

c.1648C>T · rs375691699 · VCV2570314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00987%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3829	ambiguous
REVEL	0.522	indeterminate
SaProt	LLR -5.99	tolerated
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 75 kb · p 0.00015 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P499S vs ClinVar P550S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00987% European (non-Finnish) · 116/1,175,536 alleles

Filtering AF 0.00837% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00754% 121/1,604,808 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00987%	10,134
Remaining individualsnot grpmax-eligible	0.00805%	12,426

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: ASIC2
Protein: p.Pro550Ser
Coding: c.1648C>T
MANE Select: NM_183377
dbSNP: rs375691699
Type: single nucleotide variant
Location: chr17:33014009 (GRCh38)
Gene constraint: LOEUF 0.591 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 1 PDB

Full ASIC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASIC2 c.988-4G>A Benign ★★ same type
ASIC2 p.Ala293= Benign ★★ same type
ASIC2 p.Ala129Thr Uncertain significance ★ ⚠ same type
ASIC2 p.Ala136Val Uncertain significance ★ ⚠ same type
ASIC2 p.Ala28Glu Uncertain significance ★ same type
ASIC2 p.Ala382Val Uncertain significance ★ ⚠ same type
ASIC2 p.Ala402Val Uncertain significance ★ ⚠ same type
ASIC2 p.Ala47Thr 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/asic2-p-pro550ser (accessed [today's date]).

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