Is CD320 p.Gly135= (c.405C>T) pathogenic?

CD320 p.Gly135= (c.405C>T) is classified Likely benign in CD320 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-26). Ultra-rare (popmax 0.0117%, nfe); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Gly135= (c.405C>T)?

CD320 p.Gly135= (c.405C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Gly135= (c.405C>T) in the general population?

CD320 p.Gly135= (c.405C>T) is ultra-rare (popmax 0.0117%, nfe) (gnomAD).

CD320 p.Gly135=

c.405C>T · rs372005633 · VCV1461637

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, nfe)

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.
Splicing
SpliceAI	Δ0.54	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.6	GERP -3.7
Overall
CADD	16.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% European (non-Finnish) · 137/1,168,984 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00948%

Overall 0.00981% 156/1,590,550 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0117%	8,533
South Asian	0.0103%	9,725
Remaining individualsnot grpmax-eligible	0.00812%	12,323
Admixed American	0.00533%	18,757
African / African-American	0.00269%	37,202

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.Gly135=
Coding: c.405C>T
MANE Select: NM_016579
dbSNP: rs372005633
Type: single nucleotide variant
Location: chr19:8303952 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 135: a disulfide bond; the ldl-receptor class a 2 domain

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.Gly135Val Uncertain significance ★ ⚠ same residue
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

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-gly135 (accessed [today's date]).

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