Is CD5L p.Ser267Ala (c.799T>G) pathogenic?

CD5L p.Ser267Ala (c.799T>G) is classified Uncertain significance in CD5L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-28). AlphaMissense: ambiguous (0.3639); Very rare (popmax 0.00223%, eas).

How common is CD5L p.Ser267Ala (c.799T>G) in the general population?

CD5L p.Ser267Ala (c.799T>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD5L p.Ser267Ala (c.799T>G)?

AlphaMissense predicts ambiguous (score 0.3639) — an in-silico prediction, not a clinical call.

CD5L p.Ser267Ala

c.799T>G · rs1374202517 · VCV2530621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3639	ambiguous
REVEL	0.072	moderately benign-leaning
SaProt	LLR -8.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 9,734 bp · p 0.89 · regional, not allelic
Overall
CADD	19.09	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 0.00223% East Asian · 1/44,870 alleles

Overall 6.84e-05% 1/1,461,886 alleles · very 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.Ser267Ala
Coding: c.799T>G
MANE Select: NM_005894
dbSNP: rs1374202517
Type: single nucleotide variant
Location: chr1:157833432 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.81 · 4 PDB
Residue 267: a disulfide bond; a β-strand; the srcr 3 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-ser267ala (accessed [today's date]).

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