Is ASGR1 p.Phe130Leu (c.390C>G) pathogenic?

ASGR1 p.Phe130Leu (c.390C>G) is classified Uncertain significance in ASGR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.7644); Absent from gnomAD v4.1.

How common is ASGR1 p.Phe130Leu (c.390C>G) in the general population?

ASGR1 p.Phe130Leu (c.390C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASGR1 p.Phe130Leu (c.390C>G)?

AlphaMissense predicts likely pathogenic (score 0.7644) — an in-silico prediction, not a clinical call.

ASGR1 p.Phe130Leu

c.390C>G · VCV3952202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7644 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7644	likely pathogenic
REVEL	0.051	moderately benign-leaning
SaProt	LLR -2.86	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -2.1
Regional constraint	o/e 1.06	unconstrained · MANE · 4,901 bp · p 0.25 · regional, not allelic
Overall
CADD	2.73	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASGR1
Protein: p.Phe130Leu
Coding: c.390C>G
MANE Select: NM_001671
Type: single nucleotide variant
Location: chr17:7174426 (GRCh38)
Gene constraint: LOEUF 1.323 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 8 PDB

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-phe130leu (accessed [today's date]).

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