Is CD28 p.Asn19Asp (c.55A>G) pathogenic?

CD28 p.Asn19Asp (c.55A>G) is classified Uncertain significance in CD28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1104); Very rare (popmax 0.00393%, nfe).

How common is CD28 p.Asn19Asp (c.55A>G) in the general population?

CD28 p.Asn19Asp (c.55A>G) is very rare (popmax 0.00393%, nfe) (gnomAD).

What do computational predictors say about CD28 p.Asn19Asp (c.55A>G)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CD28 p.Asn19Asp

c.55A>G · VCV4222779

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00393%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -3.42	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 6.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.67 · regional, not allelic
Overall
CADD	18.94	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 0.00393% European (non-Finnish) · 46/1,171,662 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00269%

Overall 0.00339% 49/1,447,104 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00393%	25,471
Remaining individualsnot grpmax-eligible	0.00323%	30,931
African / African-American	0.00135%	74,336

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: CD28
Protein: p.Asn19Asp
Coding: c.55A>G
MANE Select: NM_006139
Type: single nucleotide variant
Location: chr2:203726635 (GRCh38)
Gene constraint: LOEUF 0.634 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 10 PDB

Full CD28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD28 p.Ala35= Benign ★★ same type
CD28 p.Arg203Cys Uncertain significance ★ ⚠ same type
CD28 p.Asn45Ser Uncertain significance ★ ⚠ same type
CD28 p.Gln15Arg Uncertain significance ★ ⚠ same type
CD28 p.Glu93Lys Uncertain significance ★ ⚠ same type
CD28 p.Gly83Arg Uncertain significance ★ ⚠ same type
CD28 p.Gly88Ala Uncertain significance ★ ⚠ same type
CD28 p.Ile176Phe 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/cd28-p-asn19asp (accessed [today's date]).

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