Is CD320 p.Gln8Arg (c.23A>G) pathogenic?

CD320 p.Gln8Arg (c.23A>G) is classified Benign in CD320 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0678); Common (popmax 42.4%, 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.Gln8Arg (c.23A>G)?

CD320 p.Gln8Arg (c.23A>G) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

What do computational predictors say about CD320 p.Gln8Arg (c.23A>G)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

CD320 p.Gln8Arg

Q: How common is CD320 p.Gln8Arg (c.23A>G) in the general population?

CD320 p.Gln8Arg (c.23A>G) is common (popmax 42.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.23A>G · rs2232775 · VCV136683

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 42.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -3.9
Regional constraint	o/e 1.03	unconstrained · MANE · 5,824 bp · p 0.57 · regional, not allelic
Overall
CADD	1.006	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.4% African / African-American · 31,513/74,314 alleles

Filtering AF 42% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.9%

Overall 6.56% 103,741/1,582,434 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42.4%	2
South Asian	18.7%	5
Middle Eastern	7.99%	13
Remaining individualsnot grpmax-eligible	7.74%	13
East Asian	7.4%	14
Ashkenazi Jewishnot grpmax-eligible	6.04%	17
Admixed American	5.86%	17
European (non-Finnish)	3.46%	29
Finnishnot grpmax-eligible	2.79%	36
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.Gln8Arg
Coding: c.23A>G
MANE Select: NM_016579
dbSNP: rs2232775
Type: single nucleotide variant
Location: chr19:8308268 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 8: a UniProt-annotated variant site (in)

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-gln8arg (accessed [today's date]).

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