Is CD5L p.Ala59Val (c.176C>T) pathogenic?

CD5L p.Ala59Val (c.176C>T) is classified Uncertain significance in CD5L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1693); Ultra-rare (popmax 0.024%, afr).

How common is CD5L p.Ala59Val (c.176C>T) in the general population?

CD5L p.Ala59Val (c.176C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about CD5L p.Ala59Val (c.176C>T)?

AlphaMissense predicts likely benign (score 0.1693) — an in-silico prediction, not a clinical call.

CD5L p.Ala59Val

c.176C>T · rs144956987 · VCV3140624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1693 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1693	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.88	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 0.63	GERP -0.1
Regional constraint	o/e 0.99	unconstrained · MANE · 9,734 bp · p 0.89 · regional, not allelic
Overall
CADD	14.11	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 0.024% African / African-American · 18/75,048 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0013% 21/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,169
Admixed American	0.005%	20,007

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.Ala59Val
Coding: c.176C>T
MANE Select: NM_005894
dbSNP: rs144956987
Type: single nucleotide variant
Location: chr1:157836035 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 4 PDB
Residue 59: 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.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
CD5L p.Asp54Tyr 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-ala59val (accessed [today's date]).

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