Is CD320 p.Ser2= (c.6C>T) pathogenic?

CD320 p.Ser2= (c.6C>T) is classified Likely benign in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Ultra-rare (popmax 0.0596%, amr); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Ser2= (c.6C>T)?

CD320 p.Ser2= (c.6C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Ser2= (c.6C>T) in the general population?

CD320 p.Ser2= (c.6C>T) is ultra-rare (popmax 0.0596%, amr) (gnomAD).

CD320 p.Ser2=

c.6C>T · rs749442494 · VCV1137011

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0596%, amr)

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 -2.1	GERP -3.8
Overall
CADD	2.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0596% Admixed American · 35/58,690 alleles

Filtering AF 0.044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0386%

Overall 0.00957% 152/1,587,510 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0596%	1,677
Remaining individualsnot grpmax-eligible	0.0194%	5,148
Middle Eastern	0.0166%	6,040
European (non-Finnish)	0.00869%	11,509
African / African-American	0.00269%	37,243

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.Ser2=
Coding: c.6C>T
MANE Select: NM_016579
dbSNP: rs749442494
Type: single nucleotide variant
Location: chr19:8308285 (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.Ser2Ile 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-ser2 (accessed [today's date]).

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