Is CD164L2 p.Cys88Arg (c.262T>C) pathogenic?

CD164L2 p.Cys88Arg (c.262T>C) is classified Uncertain significance in CD164L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.8433); Absent from gnomAD v4.1.

How common is CD164L2 p.Cys88Arg (c.262T>C) in the general population?

CD164L2 p.Cys88Arg (c.262T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD164L2 p.Cys88Arg (c.262T>C)?

AlphaMissense predicts likely pathogenic (score 0.8433) — an in-silico prediction, not a clinical call.

CD164L2 p.Cys88Arg

c.262T>C · VCV4222600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8433 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8433	likely pathogenic · top 1% in CD164L2
REVEL	0.637	indeterminate
SaProt	LLR -14.75	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,733 bp · p 0.73 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD164L2
Protein: p.Cys88Arg
Coding: c.262T>C
MANE Select: NM_001330448
Type: single nucleotide variant
Location: chr1:27382394 (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.Cys88Tyr Uncertain significance ★ ⚠ same residue
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

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-cys88arg (accessed [today's date]).

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