Is CD320 p.Ser280= (c.840G>A) pathogenic?

CD320 p.Ser280= (c.840G>A) is classified Benign/Likely benign in CD320 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-15). Rare (popmax 0.873%, afr); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Ser280= (c.840G>A)?

CD320 p.Ser280= (c.840G>A) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Ser280= (c.840G>A) in the general population?

CD320 p.Ser280= (c.840G>A) is rare (popmax 0.873%, afr) (gnomAD).

CD320 p.Ser280=

c.840G>A · rs2232787 · VCV381271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.873%, 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.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.2	GERP -4
Overall
CADD	0.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.873% African / African-American · 655/75,032 alleles

Filtering AF 0.818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.796%

Overall 0.0487% 786/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.873%	115
Middle Eastern	0.066%	1,516
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0496%	2,016
East Asian	0.0156%	6,412
European (non-Finnish)	0.00475%	21,072
South Asian	0.0011%	91,084

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.Ser280=
Coding: c.840G>A
MANE Select: NM_016579
dbSNP: rs2232787
Type: single nucleotide variant
Location: chr19:8302472 (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.Ser280Leu 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-ser280 (accessed [today's date]).

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