Is CD320 c.502+12C>T pathogenic?

CD320 c.502+12C>T is classified Likely benign in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Very rare (popmax 0.007%, eas); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 c.502+12C>T?

CD320 c.502+12C>T is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 c.502+12C>T in the general population?

CD320 c.502+12C>T is very rare (popmax 0.007%, eas) (gnomAD).

CD320 c.502+12C>T

VCV3613138

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.007%, eas)

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
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -3.7
Overall
CADD	1.947	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.007% East Asian · 3/42,838 alleles

Filtering AF 0.00186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00101%

Overall 0.000319% 5/1,566,094 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.007%	14,279
European (non-Finnish)	0.000174%	576,193

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
Coding: c.502+12C>T
MANE Select: NM_016579
Type: single nucleotide variant
Location: chr19:8303843 (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-c-502-plus-12c-t (accessed [today's date]).

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