Is ASGR2 p.Pro48Leu (c.143C>T) pathogenic?

ASGR2 p.Pro48Leu (c.143C>T) is classified Uncertain significance in ASGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0826); Ultra-rare (popmax 0.0382%, amr).

How common is ASGR2 p.Pro48Leu (c.143C>T) in the general population?

ASGR2 p.Pro48Leu (c.143C>T) is ultra-rare (popmax 0.0382%, amr) (gnomAD).

What do computational predictors say about ASGR2 p.Pro48Leu (c.143C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

ASGR2 p.Pro48Leu

c.143C>T · VCV3435930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0382%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.71, phastCons 0.18
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.94 · regional, not allelic
Overall
CADD	15.38	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0382% Admixed American · 21/54,998 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00377% 60/1,591,170 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0382%	2,619
Middle Eastern	0.0332%	3,016
Remaining individualsnot grpmax-eligible	0.00647%	15,454
South Asian	0.0034%	29,384
European (non-Finnish)	0.00257%	38,979

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.Pro48Leu
Coding: c.143C>T
MANE Select: NM_001201352
Type: single nucleotide variant
Location: chr17:7108870 (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-pro48leu (accessed [today's date]).

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