Is CD163 p.Val863Met (c.2587G>A) pathogenic?

CD163 p.Val863Met (c.2587G>A) is classified Uncertain significance in CD163 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.2498); Very rare (popmax 8.47e-05%, nfe).

How common is CD163 p.Val863Met (c.2587G>A) in the general population?

CD163 p.Val863Met (c.2587G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD163 p.Val863Met (c.2587G>A)?

AlphaMissense predicts likely benign (score 0.2498) — an in-silico prediction, not a clinical call.

CD163 p.Val863Met

c.2587G>A · VCV4650416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2498	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.83	GERP 0.67, phastCons 0.035
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 1.4e-17 · regional, not allelic
Overall
CADD	22.2	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 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,872 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: CD163
Protein: p.Val863Met
Coding: c.2587G>A
MANE Select: NM_203416
Type: single nucleotide variant
Location: chr12:7485288 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.72 · 14 PDB
Residue 863: the srcr 8 domain; an α-helix

Full CD163 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD163 c.3344-24C>A Benign ★★ same type
CD163 c.3344-56G>A Likely benign ★★ same type
CD163 c.457+9T>A Benign ★★ same type
CD163 p.Asn642Lys Benign ★★ same type
CD163 p.Asn892= Benign ★★ same type
CD163 p.Cys1008= Benign ★★ same type
CD163 p.Ile342Val Benign ★★ ⚠ same type
CD163 p.Leu867= Benign ★★ 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/cd163-p-val863met (accessed [today's date]).

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