Is CD320 p.Val211= (c.633C>T) pathogenic?

CD320 p.Val211= (c.633C>T) is classified Likely benign in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.00439%, sas); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Val211= (c.633C>T)?

CD320 p.Val211= (c.633C>T) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Val211= (c.633C>T) in the general population?

CD320 p.Val211= (c.633C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

CD320 p.Val211=

c.633C>T · rs377252284 · VCV2731658

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 -1.7	GERP -1.8
Overall
CADD	1.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,076 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00242% 39/1,613,932 alleles · very rare exomes 37/1,461,844 · genomes 2/152,088 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
European (non-Finnish)	0.0028%	35,757
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00134%	74,898

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.Val211=
Coding: c.633C>T
MANE Select: NM_016579
dbSNP: rs377252284
Type: single nucleotide variant
Location: chr19:8302850 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 211: the 'disordered' region

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-val211 (accessed [today's date]).

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