Is CD164 p.Ala37Thr (c.109G>A) pathogenic?

CD164 p.Ala37Thr (c.109G>A) is classified Uncertain significance in CD164 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0618); Very rare (popmax 0.000854%, nfe).

How common is CD164 p.Ala37Thr (c.109G>A) in the general population?

CD164 p.Ala37Thr (c.109G>A) is very rare (popmax 0.000854%, nfe) (gnomAD).

What do computational predictors say about CD164 p.Ala37Thr (c.109G>A)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

CD164 p.Ala37Thr

c.109G>A · VCV4222593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000854%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.13	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 -2.9	GERP -2.5
Regional constraint	o/e 1.21	unconstrained · MANE · 14 kb · p 0.001 · regional, not allelic
Overall
CADD	0.112	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 0.000854% European (non-Finnish) · 10/1,170,734 alleles

Filtering AF 0.000432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000315%

Overall 0.000629% 10/1,589,750 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: CD164
Protein: p.Ala37Thr
Coding: c.109G>A
MANE Select: NM_006016
Type: single nucleotide variant
Location: chr6:109382270 (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-ala37thr (accessed [today's date]).

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