Is CD5L p.Asp54Tyr (c.160G>T) pathogenic?

CD5L p.Asp54Tyr (c.160G>T) is classified Uncertain significance in CD5L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.7356); Ultra-rare (popmax 0.045%, sas).

How common is CD5L p.Asp54Tyr (c.160G>T) in the general population?

CD5L p.Asp54Tyr (c.160G>T) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about CD5L p.Asp54Tyr (c.160G>T)?

AlphaMissense predicts likely pathogenic (score 0.7356) — an in-silico prediction, not a clinical call.

CD5L p.Asp54Tyr

c.160G>T · rs777300016 · VCV2520233

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7356	likely pathogenic
REVEL	0.136	moderately benign-leaning
SaProt	LLR -13.45	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.039	GERP -0.042, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 9,734 bp · p 0.89 · regional, not allelic
Overall
CADD	20.9	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 0.045% South Asian · 41/91,082 alleles

Filtering AF 0.034% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00254% 41/1,614,046 alleles · ultra-rare

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: CD5L
Protein: p.Asp54Tyr
Coding: c.160G>T
MANE Select: NM_005894
dbSNP: rs777300016
Type: single nucleotide variant
Location: chr1:157836051 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 4 PDB
Residue 54: the srcr 1 domain; a disulfide bond

Full CD5L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD5L p.Ala172Ser Uncertain significance ★ ⚠ same type
CD5L p.Ala342Ser Uncertain significance ★ ⚠ same type
CD5L p.Ala59Val Uncertain significance ★ ⚠ same type
CD5L p.Arg150Leu Uncertain significance ★ ⚠ same type
CD5L p.Arg198Leu Uncertain significance ★ ⚠ same type
CD5L p.Arg328Ile Uncertain significance ★ ⚠ same type
CD5L p.Asn272Ser Uncertain significance ★ ⚠ same type
CD5L p.Asn272Thr 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/cd5l-p-asp54tyr (accessed [today's date]).

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