Is CD164 p.Phe181Leu (c.541T>C) pathogenic?

CD164 p.Phe181Leu (c.541T>C) is classified Uncertain significance in CD164 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.9936); Ultra-rare (popmax 0.0134%, afr).

How common is CD164 p.Phe181Leu (c.541T>C) in the general population?

CD164 p.Phe181Leu (c.541T>C) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about CD164 p.Phe181Leu (c.541T>C)?

AlphaMissense predicts likely pathogenic (score 0.9936) — an in-silico prediction, not a clinical call.

CD164 p.Phe181Leu

c.541T>C · rs773099923 · VCV3140332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9936	likely pathogenic · top 3% in CD164
REVEL	0.704	pathogenic-leaning
SaProt	LLR -13.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 14 kb · p 0.001 · regional, not allelic
Overall
CADD	22.4	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 0.0134% African / African-American · 10/74,900 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000806% 13/1,613,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,490
Remaining individualsnot grpmax-eligible	0.0032%	31,227
Admixed American	0.00167%	59,826

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.Phe181Leu
Coding: c.541T>C
MANE Select: NM_006016
dbSNP: rs773099923
Type: single nucleotide variant
Location: chr6:109368904 (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.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.Leu183Pro 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-phe181leu (accessed [today's date]).

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