Is CD320 p.Leu253= (c.759C>T) pathogenic?

CD320 p.Leu253= (c.759C>T) is classified Benign/Likely benign in CD320 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). Rare (popmax 0.251%, sas); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Leu253= (c.759C>T)?

CD320 p.Leu253= (c.759C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Leu253= (c.759C>T) in the general population?

CD320 p.Leu253= (c.759C>T) is rare (popmax 0.251%, sas) (gnomAD).

CD320 p.Leu253=

c.759C>T · rs200607555 · VCV512916

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.251%, sas)

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.
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -1.2, phastCons 0.004
Overall
CADD	1.589	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.251% South Asian · 229/91,088 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.214%

Overall 0.0288% 465/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.251%	398
East Asian	0.209%	477
Ashkenazi Jewishnot grpmax-eligible	0.132%	759
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.00602%	16,619
Admixed American	0.005%	20,005

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.Leu253=
Coding: c.759C>T
MANE Select: NM_016579
dbSNP: rs200607555
Type: single nucleotide variant
Location: chr19:8302553 (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-leu253 (accessed [today's date]).

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