Is CD320 p.Leu205= (c.613C>T) pathogenic?

CD320 p.Leu205= (c.613C>T) is classified Likely benign in CD320 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-27). Ultra-rare (popmax 0.0187%, afr); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Leu205= (c.613C>T)?

CD320 p.Leu205= (c.613C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Leu205= (c.613C>T) in the general population?

CD320 p.Leu205= (c.613C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

CD320 p.Leu205=

c.613C>T · rs139075923 · VCV3039660

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -1.4, phastCons 0.006
Overall
CADD	0.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,012 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.000929% 15/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,358
Admixed American	0.00167%	60,006

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.Leu205=
Coding: c.613C>T
MANE Select: NM_016579
dbSNP: rs139075923
Type: single nucleotide variant
Location: chr19:8302870 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 205: the 'disordered' region

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-leu205 (accessed [today's date]).

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