Is ASGR2 p.Arg89Trp (c.265C>T) pathogenic?

ASGR2 p.Arg89Trp (c.265C>T) is classified Uncertain significance in ASGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0764); Very rare (popmax 0.00552%, nfe).

How common is ASGR2 p.Arg89Trp (c.265C>T) in the general population?

ASGR2 p.Arg89Trp (c.265C>T) is very rare (popmax 0.00552%, nfe) (gnomAD).

What do computational predictors say about ASGR2 p.Arg89Trp (c.265C>T)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

ASGR2 p.Arg89Trp

c.265C>T · rs773055006 · VCV2267645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00552%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.97	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 0.58	GERP -0.42
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.94 · regional, not allelic
Overall
CADD	11.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R94W vs ClinVar R89W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00552% European (non-Finnish) · 65/1,177,914 alleles

Filtering AF 0.00444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00404%

Overall 0.00441% 71/1,608,856 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00552%	18,122
African / African-American	0.00534%	18,724
East Asian	0.00223%	44,754
Remaining individualsnot grpmax-eligible	0.00161%	62,288

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: ASGR2
Protein: p.Arg89Trp
Coding: c.265C>T
MANE Select: NM_001201352
dbSNP: rs773055006
Type: single nucleotide variant
Location: chr17:7108534 (GRCh38)
Gene constraint: LOEUF 1.365 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 1 PDB

Full ASGR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASGR2 p.Gly303= Benign ★★ same type
ASGR2 p.Thr302= Benign ★★ same type
ASGR2 c.241+11C>A Uncertain significance ★ ⚠ same type
ASGR2 p.Ala108Pro Uncertain significance ★ ⚠ same type
ASGR2 p.Ala108Thr Uncertain significance ★ ⚠ same type
ASGR2 p.Arg153Cys Uncertain significance ★ ⚠ same type
ASGR2 p.Arg169Lys Uncertain significance ★ ⚠ same type
ASGR2 p.Arg248Lys 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/asgr2-p-arg89trp (accessed [today's date]).

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