Is CD320 p.Ser161= (c.483C>T) pathogenic?

CD320 p.Ser161= (c.483C>T) is classified Benign in CD320 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 30.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Ser161= (c.483C>T)?

CD320 p.Ser161= (c.483C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

CD320 p.Ser161=

Q: How common is CD320 p.Ser161= (c.483C>T) in the general population?

CD320 p.Ser161= (c.483C>T) is common (popmax 30.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.483C>T · rs2232784 · VCV136681

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 30.7%, afr) — too common for a highly-penetrant pathogenic allele

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 3.5	GERP -2.5, phastCons 1
Overall
CADD	6.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.7% African / African-American · 22,914/74,724 alleles

Filtering AF 30.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.2%

Overall 5.02% 80,495/1,602,380 alleles · common exomes 63,056/1,450,078 · genomes 17,439/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.7%	3
East Asian	7.39%	14
Middle Eastern	6.65%	15
Remaining individualsnot grpmax-eligible	6.08%	16
Ashkenazi Jewishnot grpmax-eligible	6.05%	17
Admixed American	5.3%	19
South Asian	3.44%	29
European (non-Finnish)	3.44%	29
Finnishnot grpmax-eligible	2.85%	35
Amishnot grpmax-eligible	2.3%	43

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.Ser161=
Coding: c.483C>T
MANE Select: NM_016579
dbSNP: rs2232784
Type: single nucleotide variant
Location: chr19:8303874 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 161: 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.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-ser161 (accessed [today's date]).

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