Is CD320 p.Arg254= (c.760C>A) pathogenic?

CD320 p.Arg254= (c.760C>A) is classified Uncertain significance in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Absent from gnomAD v4.1; Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Arg254= (c.760C>A)?

CD320 p.Arg254= (c.760C>A) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Arg254= (c.760C>A) in the general population?

CD320 p.Arg254= (c.760C>A) is absent from gnomAD v4.1 (gnomAD).

CD320 p.Arg254=

c.760C>A · rs750760449 · VCV851092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.027	moderately benign-leaning
Splicing
SpliceAI	Δ0.67	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.2	GERP -1.4, phastCons 0.001
Overall
CADD	16.49	PHRED · no single calibrated threshold — expert panels disagree

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: CD320
Protein: p.Arg254=
Coding: c.760C>A
MANE Select: NM_016579
dbSNP: rs750760449
Type: single nucleotide variant
Location: chr19:8302552 (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.Arg254Gln Uncertain significance ★★ ⚠ same residue
CD320 p.Arg254Ter Uncertain significance ★ same residue
CD320 p.Arg129Leu Uncertain significance ★★ ⚠ same condition
CD320 p.Arg138Ser 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

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-arg254 (accessed [today's date]).

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