Is CD8B p.Leu183Pro (c.548T>C) pathogenic?

CD8B p.Leu183Pro (c.548T>C) is classified Uncertain significance in CD8B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: ambiguous (0.5102); Very rare (popmax 0.00179%, amr).

How common is CD8B p.Leu183Pro (c.548T>C) in the general population?

CD8B p.Leu183Pro (c.548T>C) is very rare (popmax 0.00179%, amr) (gnomAD).

What do computational predictors say about CD8B p.Leu183Pro (c.548T>C)?

AlphaMissense predicts ambiguous (score 0.5102) — an in-silico prediction, not a clinical call.

CD8B p.Leu183Pro

c.548T>C · VCV4650744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, amr)

Computational evidence

Protein change
AlphaMissense	0.5102	ambiguous
REVEL	0.339	indeterminate
SaProt	LLR -12.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 20 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	25.9	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 0.00179% Admixed American · 1/55,726 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000209% 3/1,432,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00179%	55,726
European (non-Finnish)	0.000172%	582,571

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.Leu183Pro
Coding: c.548T>C
MANE Select: NM_004931
Type: single nucleotide variant
Location: chr2:86846719 (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-leu183pro (accessed [today's date]).

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