Is CD320 p.Val185fs (c.551dup) pathogenic?

CD320 p.Val185fs (c.551dup) is classified Uncertain significance in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). Very rare (popmax 0.00619%, nfe); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Val185fs (c.551dup)?

CD320 p.Val185fs (c.551dup) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Val185fs (c.551dup) in the general population?

CD320 p.Val185fs (c.551dup) is very rare (popmax 0.00619%, nfe) (gnomAD).

CD320 p.Val185fs

c.551dup · VCV4740047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00619%, nfe)

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.54	GERP 0.08
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	TGTGGCATTCCCGACAGAGGGGACACTCTCCAGGGTCACAGGGGGCCCCATGGT simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00619% European (non-Finnish) · 73/1,180,022 alleles

Filtering AF 0.00503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00462%

Overall 0.00477% 77/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00619%	16,165
African / African-American	0.004%	24,972
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Val185fs
Coding: c.551dup
MANE Select: NM_016579
Type: Duplication
Location: chr19:8302931 (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.Val185= Likely benign ★ same residue
CD320 p.Val208_Pro209insThrSerLeuArgAsnAlaThrThrMetGlyProProValThrLeuGluSerVal Uncertain significance ★ same condition
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

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-val185fs (accessed [today's date]).

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