Is CD5L p.Val162Glu (c.485T>A) pathogenic?

CD5L p.Val162Glu (c.485T>A) is classified Uncertain significance in CD5L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.9569); Very rare (popmax 0.00167%, amr).

How common is CD5L p.Val162Glu (c.485T>A) in the general population?

CD5L p.Val162Glu (c.485T>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD5L p.Val162Glu (c.485T>A)?

AlphaMissense predicts likely pathogenic (score 0.9569) — an in-silico prediction, not a clinical call.

CD5L p.Val162Glu

c.485T>A · VCV4650670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9569	likely pathogenic · top 7% in CD5L
REVEL	0.306	indeterminate
SaProt	LLR -13.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 9,734 bp · p 0.89 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/60,002 alleles

Overall 0.00131% 2/152,178 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	8.47e-05%	1,180,043

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.Val162Glu
Coding: c.485T>A
MANE Select: NM_005894
Type: single nucleotide variant
Location: chr1:157834640 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 4 PDB
Residue 162: the srcr 2 domain

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-val162glu (accessed [today's date]).

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