Is CD320 p.Ser241Asn (c.722G>A) pathogenic?

CD320 p.Ser241Asn (c.722G>A) is classified Likely benign in CD320 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-27). AlphaMissense: likely pathogenic (0.5959); Rare (popmax 0.155%, afr); Associated with methylmalonic acidemia due to transcobalamin receptor defect.

What condition is associated with CD320 p.Ser241Asn (c.722G>A)?

CD320 p.Ser241Asn (c.722G>A) is associated with methylmalonic acidemia due to transcobalamin receptor defect (ClinVar).

How common is CD320 p.Ser241Asn (c.722G>A) in the general population?

CD320 p.Ser241Asn (c.722G>A) is rare (popmax 0.155%, afr) (gnomAD).

What do computational predictors say about CD320 p.Ser241Asn (c.722G>A)?

AlphaMissense predicts likely pathogenic (score 0.5959) — an in-silico prediction, not a clinical call.

CD320 p.Ser241Asn

c.722G>A · rs140803270 · VCV760688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5959 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.155%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

methylmalonic acidemia due to transcobalamin receptor defect

Computational evidence

Protein change
AlphaMissense	0.5959	likely pathogenic
REVEL	0.218	benign-leaning
SaProt	LLR -11.13	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.034	GERP -2.3
Regional constraint	o/e 1.03	unconstrained · MANE · 5,824 bp · p 0.57 · regional, not allelic
Overall
CADD	6.418	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 0.155% African / African-American · 116/75,022 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.00768% 124/1,613,730 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.155%	647
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.00017%	589,943

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.Ser241Asn
Coding: c.722G>A
MANE Select: NM_016579
dbSNP: rs140803270
Type: single nucleotide variant
Location: chr19:8302590 (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.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-ser241asn (accessed [today's date]).

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