Is ASGR1 p.Pro241Arg (c.722C>G) pathogenic?

ASGR1 p.Pro241Arg (c.722C>G) is classified Uncertain significance in ASGR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.9718); Very rare (popmax 0.00667%, amr).

How common is ASGR1 p.Pro241Arg (c.722C>G) in the general population?

ASGR1 p.Pro241Arg (c.722C>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ASGR1 p.Pro241Arg (c.722C>G)?

AlphaMissense predicts likely pathogenic (score 0.9718) — an in-silico prediction, not a clinical call.

ASGR1 p.Pro241Arg

c.722C>G · VCV3789331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9718	likely pathogenic · top 7% in ASGR1
REVEL	0.732	pathogenic-leaning
SaProt	LLR -13.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,901 bp · p 0.25 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00667% Admixed American · 4/59,974 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00048% 7/1,458,528 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,993
Remaining individualsnot grpmax-eligible	0.0016%	62,446
African / African-American	0.00133%	75,044
European (non-Finnish)	8.48e-05%	1,179,542

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.Pro241Arg
Coding: c.722C>G
MANE Select: NM_001671
Type: single nucleotide variant
Location: chr17:7173813 (GRCh38)
Gene constraint: LOEUF 1.323 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 8 PDB
Residue 241: a disulfide bond; 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-pro241arg (accessed [today's date]).

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