Is CD53 p.Asp120Asn (c.358G>A) pathogenic?

CD53 p.Asp120Asn (c.358G>A) is classified Uncertain significance in CD53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1168); Very rare (popmax 0.005%, amr).

How common is CD53 p.Asp120Asn (c.358G>A) in the general population?

CD53 p.Asp120Asn (c.358G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CD53 p.Asp120Asn (c.358G>A)?

AlphaMissense predicts likely benign (score 0.1168) — an in-silico prediction, not a clinical call.

CD53 p.Asp120Asn

c.358G>A · VCV3998276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1168 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1168	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -8.32	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 1.1	GERP -3.2, phastCons 0.023
Regional constraint	o/e 0.82	unconstrained · MANE · 7,783 bp · p 0.0032 · regional, not allelic
Overall
CADD	7.193	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,032 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00118% 19/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,011
Remaining individualsnot grpmax-eligible	0.0032%	31,247
Finnishnot grpmax-eligible	0.00156%	64,008
African / African-American	0.00133%	75,014
European (non-Finnish)	0.00102%	98,327

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: CD53
Protein: p.Asp120Asn
Coding: c.358G>A
MANE Select: NM_000560
Type: single nucleotide variant
Location: chr1:110894990 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB
Residue 120: an α-helix

Full CD53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD53 p.Ala172Val Uncertain significance ★ ⚠ same type
CD53 p.Arg124His Uncertain significance ★ ⚠ same type
CD53 p.Gly117Asp Uncertain significance ★ ⚠ same type
CD53 p.Gly117Val Uncertain significance ★ ⚠ same type
CD53 p.Gly156Ser Uncertain significance ★ ⚠ same type
CD53 p.His45Arg Uncertain significance ★ ⚠ same type
CD53 p.Ile122Thr Uncertain significance ★ ⚠ same type
CD53 p.Ile185Val Uncertain significance ★ ⚠ same type

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/cd53-p-asp120asn (accessed [today's date]).

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