Is CD164L2 p.Arg43Pro (c.128G>C) pathogenic?

CD164L2 p.Arg43Pro (c.128G>C) is classified Uncertain significance in CD164L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.2254); Very rare (popmax 0.00161%, nfe).

How common is CD164L2 p.Arg43Pro (c.128G>C) in the general population?

CD164L2 p.Arg43Pro (c.128G>C) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about CD164L2 p.Arg43Pro (c.128G>C)?

AlphaMissense predicts likely benign (score 0.2254) — an in-silico prediction, not a clinical call.

CD164L2 p.Arg43Pro

c.128G>C · VCV3998016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2254	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -5.41	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 1.6	GERP 1.8, phastCons 0.9
Regional constraint	o/e 1.02	unconstrained · MANE · 3,733 bp · p 0.73 · regional, not allelic
Overall
CADD	24.3	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 0.00161% European (non-Finnish) · 19/1,179,844 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 19/1,460,540 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: CD164L2
Protein: p.Arg43Pro
Coding: c.128G>C
MANE Select: NM_001330448
Type: single nucleotide variant
Location: chr1:27382628 (GRCh38)
Gene constraint: LOEUF 1.268 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70

Full CD164L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD164L2 p.Ala132Thr Uncertain significance ★ ⚠ same type
CD164L2 p.Ala24Thr Uncertain significance ★ same type
CD164L2 p.Ala24Val Uncertain significance ★ ⚠ same type
CD164L2 p.Ala40Ser Uncertain significance ★ ⚠ same type
CD164L2 p.Ala53Thr Uncertain significance ★ ⚠ same type
CD164L2 p.Arg104Leu Uncertain significance ★ ⚠ same type
CD164L2 p.Arg10Pro Uncertain significance ★ ⚠ same type
CD164L2 p.Arg7Cys 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/cd164l2-p-arg43pro (accessed [today's date]).

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