Is CD5 p.Ala492Asp (c.1475C>A) pathogenic?

CD5 p.Ala492Asp (c.1475C>A) is classified Uncertain significance in CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.4457); Ultra-rare (popmax 0.0814%, afr).

How common is CD5 p.Ala492Asp (c.1475C>A) in the general population?

CD5 p.Ala492Asp (c.1475C>A) is ultra-rare (popmax 0.0814%, afr) (gnomAD).

What do computational predictors say about CD5 p.Ala492Asp (c.1475C>A)?

AlphaMissense predicts ambiguous (score 0.4457) — an in-silico prediction, not a clinical call.

CD5 p.Ala492Asp

c.1475C>A · VCV4222951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0814%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4457	ambiguous
REVEL	0.215	benign-leaning
SaProt	LLR -6.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.42, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 23 kb · p 0.00031 · regional, not allelic
Overall
CADD	22.7	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 0.0814% African / African-American · 61/74,916 alleles

Filtering AF 0.065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0591%

Overall 0.00491% 79/1,609,990 alleles · ultra-rare exomes 44/1,457,750 · genomes 35/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0814%	1,228
Middle Eastern	0.0497%	2,011
Admixed American	0.0151%	6,643
Remaining individualsnot grpmax-eligible	0.00964%	10,378

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.Ala492Asp
Coding: c.1475C>A
MANE Select: NM_014207
Type: single nucleotide variant
Location: chr11:61125826 (GRCh38)
Gene constraint: LOEUF 0.835 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32 · 4 PDB
Residue 492: the 'disordered' region

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

Similar variants

CD5 p.Ala492Val Uncertain significance ★ ⚠ same residue
CD5 p.Ala471Val Benign ★★ same type
CD5 p.Pro224Leu Benign ★★ same type
CD5 p.Ala295Ser 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
CD5 p.Arg39Cys 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-ala492asp (accessed [today's date]).

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