Is CD8B p.Ser20Leu (c.59C>T) pathogenic?

CD8B p.Ser20Leu (c.59C>T) is classified Uncertain significance in CD8B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.1021); Very rare (popmax 0.0006%, nfe).

How common is CD8B p.Ser20Leu (c.59C>T) in the general population?

CD8B p.Ser20Leu (c.59C>T) is very rare (popmax 0.0006%, nfe) (gnomAD).

What do computational predictors say about CD8B p.Ser20Leu (c.59C>T)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

CD8B p.Ser20Leu

c.59C>T · VCV3488207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0006%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.97	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 -0.099
Regional constraint	o/e 0.72	unconstrained · MANE · 20 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	3.046	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 0.0006% European (non-Finnish) · 7/1,166,494 alleles

Filtering AF 0.00025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000161%

Overall 0.00044% 7/1,592,134 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: CD8B
Protein: p.Ser20Leu
Coding: c.59C>T
MANE Select: NM_004931
Type: single nucleotide variant
Location: chr2:86858401 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.03

Full CD8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD8B p.Ala190Thr Uncertain significance ★ ⚠ same type
CD8B p.Ala60Thr Uncertain significance ★ ⚠ same type
CD8B p.Arg156Trp Uncertain significance ★ ⚠ same type
CD8B p.Arg201Gln Uncertain significance ★ ⚠ same type
CD8B p.Arg203Cys Uncertain significance ★ ⚠ same type
CD8B p.Arg51His Uncertain significance ★ ⚠ same type
CD8B p.Arg98Gln Uncertain significance ★ ⚠ same type
CD8B p.Arg98Leu 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/cd8b-p-ser20leu (accessed [today's date]).

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