Is CD163 p.Val628Ile (c.1882G>A) pathogenic?

CD163 p.Val628Ile (c.1882G>A) is classified Uncertain significance in CD163 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0735); Absent from gnomAD v4.1.

How common is CD163 p.Val628Ile (c.1882G>A) in the general population?

CD163 p.Val628Ile (c.1882G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD163 p.Val628Ile (c.1882G>A)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

CD163 p.Val628Ile

c.1882G>A · VCV4222553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.66	GERP -2.1, phastCons 0.001
Regional constraint	o/e 0.77	unconstrained · MANE · 24 kb · p 1.4e-17 · regional, not allelic
Overall
CADD	12.95	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD163
Protein: p.Val628Ile
Coding: c.1882G>A
MANE Select: NM_203416
Type: single nucleotide variant
Location: chr12:7487527 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.72 · 14 PDB
Residue 628: the srcr 6 domain; a β-strand; a disulfide bond

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-val628ile (accessed [today's date]).

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