Is CD5 p.Ala492Val (c.1475C>T) pathogenic?

CD5 p.Ala492Val (c.1475C>T) is classified Uncertain significance in CD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1627); Ultra-rare (popmax 0.0672%, eas).

How common is CD5 p.Ala492Val (c.1475C>T) in the general population?

CD5 p.Ala492Val (c.1475C>T) is ultra-rare (popmax 0.0672%, eas) (gnomAD).

What do computational predictors say about CD5 p.Ala492Val (c.1475C>T)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

CD5 p.Ala492Val

c.1475C>T · rs200138022 · VCV3140611

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0672%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -5.96	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 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

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 0.0672% East Asian · 30/44,638 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0419%

Overall 0.00193% 31/1,609,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0672%	1,488
Admixed American	0.00167%	59,790

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.Ala492Val
Coding: c.1475C>T
MANE Select: NM_014207
dbSNP: rs200138022
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.Ala492Asp 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-ala492val (accessed [today's date]).

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