Is CD8B p.Pro170Ala (c.508C>G) pathogenic?

CD8B p.Pro170Ala (c.508C>G) is classified Uncertain significance in CD8B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.0941); Ultra-rare (popmax 0.0382%, amr).

How common is CD8B p.Pro170Ala (c.508C>G) in the general population?

CD8B p.Pro170Ala (c.508C>G) is ultra-rare (popmax 0.0382%, amr) (gnomAD).

What do computational predictors say about CD8B p.Pro170Ala (c.508C>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

CD8B p.Pro170Ala

c.508C>G · rs779524372 · VCV2340963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0382%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -5.24	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 0.061
Regional constraint	o/e 0.72	unconstrained · MANE · 20 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	9.754	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 0.0382% Admixed American · 21/54,918 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00266% 42/1,579,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0382%	2,615
Middle Eastern	0.0331%	3,021
Remaining individualsnot grpmax-eligible	0.0049%	20,411
Ashkenazi Jewishnot grpmax-eligible	0.00345%	28,950
African / African-American	0.00135%	74,176
South Asian	0.00116%	86,088
European (non-Finnish)	0.00112%	89,375

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.Pro170Ala
Coding: c.508C>G
MANE Select: NM_004931
dbSNP: rs779524372
Type: single nucleotide variant
Location: chr2:86846759 (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-pro170ala (accessed [today's date]).

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