Is LMAN2 p.Asp76Ala (c.227A>C) pathogenic?

LMAN2 p.Asp76Ala (c.227A>C) is classified Uncertain significance in LMAN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: ambiguous (0.5316); Absent from gnomAD v4.1.

How common is LMAN2 p.Asp76Ala (c.227A>C) in the general population?

LMAN2 p.Asp76Ala (c.227A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LMAN2 p.Asp76Ala (c.227A>C)?

AlphaMissense predicts ambiguous (score 0.5316) — an in-silico prediction, not a clinical call.

LMAN2 p.Asp76Ala

c.227A>C · rs764703405 · VCV2325534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5316 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5316	ambiguous
REVEL	0.531	indeterminate
SaProt	LLR -13.34	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.61 · regional, not allelic
Overall
CADD	33.0	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: LMAN2
Protein: p.Asp76Ala
Coding: c.227A>C
MANE Select: NM_006816
dbSNP: rs764703405
Type: single nucleotide variant
Location: chr5:177351261 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.45
Residue 76: the l-type lectin-like domain

Full LMAN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LMAN2 p.Ala134Thr Uncertain significance ★ ⚠ same type
LMAN2 p.Ala200Val Uncertain significance ★ same type
LMAN2 p.Ala44Ser Uncertain significance ★ ⚠ same type
LMAN2 p.Arg139Gln Uncertain significance ★ ⚠ same type
LMAN2 p.Arg139Trp Uncertain significance ★ ⚠ same type
LMAN2 p.Arg141Cys Uncertain significance ★ same type
LMAN2 p.Arg172His Uncertain significance ★ ⚠ same type
LMAN2 p.Arg195Cys 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/lman2-p-asp76ala (accessed [today's date]).

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