Is ASGR2 p.Leu64Pro (c.191T>C) pathogenic?

ASGR2 p.Leu64Pro (c.191T>C) is classified Uncertain significance in ASGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: ambiguous (0.3644); Very rare (popmax 6.84e-05%).

How common is ASGR2 p.Leu64Pro (c.191T>C) in the general population?

ASGR2 p.Leu64Pro (c.191T>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ASGR2 p.Leu64Pro (c.191T>C)?

AlphaMissense predicts ambiguous (score 0.3644) — an in-silico prediction, not a clinical call.

ASGR2 p.Leu64Pro

c.191T>C · rs2507739788 · VCV2615982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Computational evidence

Protein change
AlphaMissense	0.3644	ambiguous
REVEL	0.337	indeterminate
SaProt	LLR -14.40	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.94 · regional, not allelic
Overall
CADD	24.9	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 6.84e-05%

Overall 6.84e-05% 1/1,461,768 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: ASGR2
Protein: p.Leu64Pro
Coding: c.191T>C
MANE Select: NM_001201352
dbSNP: rs2507739788
Type: single nucleotide variant
Location: chr17:7108822 (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-leu64pro (accessed [today's date]).

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