Is CD164 p.Val20Leu (c.58G>T) pathogenic?

CD164 p.Val20Leu (c.58G>T) is classified Uncertain significance in CD164 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1172); Rare (popmax 0.113%, afr).

How common is CD164 p.Val20Leu (c.58G>T) in the general population?

CD164 p.Val20Leu (c.58G>T) is rare (popmax 0.113%, afr) (gnomAD).

What do computational predictors say about CD164 p.Val20Leu (c.58G>T)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

CD164 p.Val20Leu

c.58G>T · rs138925698 · VCV1467238

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.26	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 0.58	GERP 0.7, phastCons 0.46
Regional constraint	o/e 1.21	unconstrained · MANE · 14 kb · p 0.001 · regional, not allelic
Overall
CADD	12.9	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 0.113% African / African-American · 84/74,260 alleles

Filtering AF 0.0936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0864%

Overall 0.00654% 103/1,574,642 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.113%	884
Admixed American	0.0275%	3,638
Remaining individualsnot grpmax-eligible	0.00653%	15,304

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.Val20Leu
Coding: c.58G>T
MANE Select: NM_006016
dbSNP: rs138925698
Type: single nucleotide variant
Location: chr6:109382321 (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-val20leu (accessed [today's date]).

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