Is CD320 p.Asn126= (c.378C>T) pathogenic?

CD320 p.Asn126= (c.378C>T) is classified Likely benign in CD320 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-23). Ultra-rare (popmax 0.0371%, nfe); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Asn126= (c.378C>T)?

CD320 p.Asn126= (c.378C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Asn126= (c.378C>T) in the general population?

CD320 p.Asn126= (c.378C>T) is ultra-rare (popmax 0.0371%, nfe) (gnomAD).

CD320 p.Asn126=

c.378C>T · rs144097701 · VCV1536736

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0371%, nfe)

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.42 · evaluated, not missing
Pangolin	Δ0.46	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 6.9	GERP 0.86, phastCons 1
Overall
CADD	10.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0371% European (non-Finnish) · 431/1,161,782 alleles

Filtering AF 0.0342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.0283% 447/1,577,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0371%	2,696
Remaining individualsnot grpmax-eligible	0.0147%	6,795
Admixed American	0.00555%	18,015
Finnishnot grpmax-eligible	0.00489%	20,445
African / African-American	0.00135%	74,180

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.Asn126=
Coding: c.378C>T
MANE Select: NM_016579
dbSNP: rs144097701
Type: single nucleotide variant
Location: chr19:8303979 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB

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-asn126 (accessed [today's date]).

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