Is CD320 p.Val68Met (c.202G>A) pathogenic?

CD320 p.Val68Met (c.202G>A) is classified Uncertain significance in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely pathogenic (0.5848); Very rare (popmax 0.0017%, nfe); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Val68Met (c.202G>A)?

CD320 p.Val68Met (c.202G>A) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Val68Met (c.202G>A) in the general population?

CD320 p.Val68Met (c.202G>A) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about CD320 p.Val68Met (c.202G>A)?

AlphaMissense predicts likely pathogenic (score 0.5848) — an in-silico prediction, not a clinical call.

CD320 p.Val68Met

c.202G>A · rs748020753 · VCV661454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
AlphaMissense	0.5848	likely pathogenic
REVEL	0.467	indeterminate
SaProt	LLR -9.24	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -4.8
Regional constraint	o/e 1.03	unconstrained · MANE · 5,824 bp · p 0.57 · regional, not allelic
Overall
CADD	13.64	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 0.0017% European (non-Finnish) · 20/1,179,898 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.0013% 21/1,613,018 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,995
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Val68Met
Coding: c.202G>A
MANE Select: NM_016579
dbSNP: rs748020753
Type: single nucleotide variant
Location: chr19:8305097 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61 · 6 PDB
Residue 68: a disulfide bond; a β-strand; the ldl-receptor class a 1 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-val68met (accessed [today's date]).

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