Is ASGR2 p.Glu271Lys (c.811G>A) pathogenic?

ASGR2 p.Glu271Lys (c.811G>A) is classified Uncertain significance in ASGR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.38); Very rare (popmax 0.000169%, nfe).

How common is ASGR2 p.Glu271Lys (c.811G>A) in the general population?

ASGR2 p.Glu271Lys (c.811G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about ASGR2 p.Glu271Lys (c.811G>A)?

AlphaMissense predicts ambiguous (score 0.38) — an in-silico prediction, not a clinical call.

ASGR2 p.Glu271Lys

c.811G>A · VCV3435935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.38 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.38	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.94 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E276K vs ClinVar E271K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,054 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00155% 25/1,614,122 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)grpmax	0.000169%	590,026

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu271Lys
Coding: c.811G>A
MANE Select: NM_001201352
Type: single nucleotide variant
Location: chr17:7101685 (GRCh38)
Gene constraint: LOEUF 1.365 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 1 PDB
Residue 271: a disulfide bond; the c-type lectin domain

Full ASGR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASGR2 p.Glu271Gln Uncertain significance ★ ⚠ same residue
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

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-glu271lys (accessed [today's date]).

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