Is ASGR1 p.Val192Ile (c.574G>A) pathogenic?

ASGR1 p.Val192Ile (c.574G>A) is classified Uncertain significance in ASGR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.0817); Very rare (popmax 0.0022%, sas).

How common is ASGR1 p.Val192Ile (c.574G>A) in the general population?

ASGR1 p.Val192Ile (c.574G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ASGR1 p.Val192Ile (c.574G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

ASGR1 p.Val192Ile

c.574G>A · rs1267248033 · VCV2490534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -4.72	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 -0.53	GERP -4
Regional constraint	o/e 1.06	unconstrained · MANE · 4,901 bp · p 0.25 · regional, not allelic
Overall
CADD	1.11	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 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,461,734 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Val192Ile
Coding: c.574G>A
MANE Select: NM_001671
dbSNP: rs1267248033
Type: single nucleotide variant
Location: chr17:7174158 (GRCh38)
Gene constraint: LOEUF 1.323 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.28 · 8 PDB
Residue 192: 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-val192ile (accessed [today's date]).

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