Is CD164 p.Leu183Pro (c.548T>C) pathogenic?

CD164 p.Leu183Pro (c.548T>C) is classified Uncertain significance in CD164 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-26). AlphaMissense: likely pathogenic (0.9867); Ultra-rare (popmax 0.0195%, nfe).

How common is CD164 p.Leu183Pro (c.548T>C) in the general population?

CD164 p.Leu183Pro (c.548T>C) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

What do computational predictors say about CD164 p.Leu183Pro (c.548T>C)?

AlphaMissense predicts likely pathogenic (score 0.9867) — an in-silico prediction, not a clinical call.

CD164 p.Leu183Pro

c.548T>C · rs147393458 · VCV1506544

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9867 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9867	likely pathogenic · top 4% in CD164
REVEL	0.575	indeterminate
SaProt	LLR -14.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 14 kb · p 0.001 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0195% European (non-Finnish) · 230/1,179,784 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.015% 242/1,613,350 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,129
African / African-American	0.0107%	9,359
Remaining individualsnot grpmax-eligible	0.0048%	20,819
Admixed American	0.00167%	59,770

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: CD164
Protein: p.Leu183Pro
Coding: c.548T>C
MANE Select: NM_006016
dbSNP: rs147393458
Type: single nucleotide variant
Location: chr6:109368897 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 67.15

Full CD164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD164 p.Leu183= Likely benign ★ same residue
CD164 p.Arg192Ter Uncertain significance ★★ same type
CD164 p.Asn121Ser Uncertain significance ★★ ⚠ same type
CD164 p.Asn32Lys Uncertain significance ★★ ⚠ same type
CD164 p.Asp107Asn Uncertain significance ★★ ⚠ same type
CD164 p.Leu15Val Uncertain significance ★★ ⚠ same type
CD164 p.Leu9Phe Uncertain significance ★★ ⚠ same type
CD164 p.Lys137Gln 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/cd164-p-leu183pro (accessed [today's date]).

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