Is CD5 p.Asp484Asn (c.1450G>A) pathogenic?

CD5 p.Asp484Asn (c.1450G>A) is classified Uncertain significance in CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-08). AlphaMissense: ambiguous (0.4861); Ultra-rare (popmax 0.0514%, eas).

How common is CD5 p.Asp484Asn (c.1450G>A) in the general population?

CD5 p.Asp484Asn (c.1450G>A) is ultra-rare (popmax 0.0514%, eas) (gnomAD).

What do computational predictors say about CD5 p.Asp484Asn (c.1450G>A)?

AlphaMissense predicts ambiguous (score 0.4861) — an in-silico prediction, not a clinical call.

CD5 p.Asp484Asn

c.1450G>A · VCV4222945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4861 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0514%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4861	ambiguous
REVEL	0.288	benign-leaning
SaProt	LLR -8.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.00031 · regional, not allelic
Overall
CADD	26.9	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 0.0514% East Asian · 23/44,788 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0297%

Overall 0.00527% 85/1,612,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0514%	1,947
South Asian	0.011%	9,091
Remaining individualsnot grpmax-eligible	0.00961%	10,408
African / African-American	0.00534%	18,737
European (non-Finnish)	0.00348%	28,762
Admixed American	0.00167%	59,924

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: CD5
Protein: p.Asp484Asn
Coding: c.1450G>A
MANE Select: NM_014207
Type: single nucleotide variant
Location: chr11:61125801 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32 · 4 PDB
Residue 484: the 'disordered' region

Full CD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD5 p.Ala471Val Benign ★★ same type
CD5 p.Pro224Leu Benign ★★ same type
CD5 p.Ala295Ser Uncertain significance ★ ⚠ same type
CD5 p.Ala492Asp Uncertain significance ★ ⚠ same type
CD5 p.Ala492Val Uncertain significance ★ ⚠ same type
CD5 p.Ala77Val Uncertain significance ★ ⚠ same type
CD5 p.Arg228Gln Uncertain significance ★ ⚠ same type
CD5 p.Arg338Gln 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/cd5-p-asp484asn (accessed [today's date]).

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