Is ASGR1 p.His161Gln (c.483C>G) pathogenic?

ASGR1 p.His161Gln (c.483C>G) is classified Uncertain significance in ASGR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.3441); Very rare (popmax 0.00223%, eas).

How common is ASGR1 p.His161Gln (c.483C>G) in the general population?

ASGR1 p.His161Gln (c.483C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ASGR1 p.His161Gln (c.483C>G)?

AlphaMissense predicts ambiguous (score 0.3441) — an in-silico prediction, not a clinical call.

ASGR1 p.His161Gln

c.483C>G · rs1176161814 · VCV3130292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3441	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -4.7
Regional constraint	o/e 1.06	unconstrained · MANE · 4,901 bp · p 0.25 · regional, not allelic
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Overall 0.000205% 3/1,461,818 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
Admixed American	0.00167%	60,016
South Asian	0.0011%	91,084

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: ASGR1
Protein: p.His161Gln
Coding: c.483C>G
MANE Select: NM_001671
dbSNP: rs1176161814
Type: single nucleotide variant
Location: chr17:7174249 (GRCh38)
Gene constraint: LOEUF 1.323 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 8 PDB
Residue 161: a disulfide bond; a β-strand; the c-type lectin domain

Full ASGR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASGR1 p.Arg183Gly Uncertain significance ★ ⚠ same type
ASGR1 p.Arg274Leu Uncertain significance ★ ⚠ same type
ASGR1 p.Asp133Val Uncertain significance ★ ⚠ same type
ASGR1 p.Asp186Glu Uncertain significance ★ ⚠ same type
ASGR1 p.Asp216Ala Uncertain significance ★ ⚠ same type
ASGR1 p.Asp243Gly Uncertain significance ★ ⚠ same type
ASGR1 p.Asp243Tyr Uncertain significance ★ ⚠ same type
ASGR1 p.Asp254Glu 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/asgr1-p-his161gln (accessed [today's date]).

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