Is ASGR1 p.Pro155Ser (c.463C>T) pathogenic?

ASGR1 p.Pro155Ser (c.463C>T) is classified Uncertain significance in ASGR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: ambiguous (0.5142); Very rare (popmax 8.47e-05%, nfe).

How common is ASGR1 p.Pro155Ser (c.463C>T) in the general population?

ASGR1 p.Pro155Ser (c.463C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ASGR1 p.Pro155Ser (c.463C>T)?

AlphaMissense predicts ambiguous (score 0.5142) — an in-silico prediction, not a clinical call.

ASGR1 p.Pro155Ser

c.463C>T · VCV3317958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5142 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5142	ambiguous
REVEL	0.352	indeterminate
SaProt	LLR -8.95	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,901 bp · p 0.25 · regional, not allelic
Overall
CADD	25.4	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 8.47e-05% European (non-Finnish) · 1/1,179,960 alleles

Overall 6.84e-05% 1/1,461,726 alleles · very rare

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.Pro155Ser
Coding: c.463C>T
MANE Select: NM_001671
Type: single nucleotide variant
Location: chr17:7174269 (GRCh38)
Gene constraint: LOEUF 1.323 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 8 PDB
Residue 155: a disulfide bond

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-pro155ser (accessed [today's date]).

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