Is CD320 p.Asp163Asn (c.487G>A) pathogenic?

CD320 p.Asp163Asn (c.487G>A) is classified Uncertain significance in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely pathogenic (0.9302); Very rare (popmax 0.00856%, amr); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Asp163Asn (c.487G>A)?

CD320 p.Asp163Asn (c.487G>A) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Asp163Asn (c.487G>A) in the general population?

CD320 p.Asp163Asn (c.487G>A) is very rare (popmax 0.00856%, amr) (gnomAD).

What do computational predictors say about CD320 p.Asp163Asn (c.487G>A)?

AlphaMissense predicts likely pathogenic (score 0.9302) — an in-silico prediction, not a clinical call.

CD320 p.Asp163Asn

c.487G>A · rs767294120 · VCV2904387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00856%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
AlphaMissense	0.9302	likely pathogenic · top 7% in CD320
REVEL	0.544	indeterminate
SaProt	LLR -10.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,824 bp · p 0.57 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00856% Admixed American · 5/58,402 alleles

Filtering AF 0.00333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.000897% 13/1,448,516 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00856%	11,680
South Asian	0.00225%	44,392
Remaining individualsnot grpmax-eligible	0.00161%	61,978
European (non-Finnish)	0.000426%	234,839

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: CD320
Protein: p.Asp163Asn
Coding: c.487G>A
MANE Select: NM_016579
dbSNP: rs767294120
Type: single nucleotide variant
Location: chr19:8303870 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 163: a binding site; a disulfide bond; an α-helix; the ldl-receptor class a 2 domain

Full CD320 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

methylmalonic acidemia due to transcobalamin receptor defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD320 p.Arg129Leu Uncertain significance ★★ ⚠ same condition
CD320 p.Arg138Ser Uncertain significance ★★ ⚠ same condition
CD320 p.Arg254Gln Uncertain significance ★★ ⚠ same condition
CD320 p.Arg258His Uncertain significance ★★ ⚠ same condition
CD320 p.Asn170Ser Uncertain significance ★★ ⚠ same condition
CD320 p.Asp143Asn Uncertain significance ★★ ⚠ same condition
CD320 p.Asp160Asn Uncertain significance ★★ ⚠ same condition
CD320 p.Gly166Val Uncertain significance ★★ ⚠ same condition

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/cd320-p-asp163asn (accessed [today's date]).

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