Is CD164L2 p.His161Asp (c.481C>G) pathogenic?

CD164L2 p.His161Asp (c.481C>G) is classified Uncertain significance in CD164L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: ambiguous (0.4215); Very rare (popmax 0.00167%, amr).

How common is CD164L2 p.His161Asp (c.481C>G) in the general population?

CD164L2 p.His161Asp (c.481C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD164L2 p.His161Asp (c.481C>G)?

AlphaMissense predicts ambiguous (score 0.4215) — an in-silico prediction, not a clinical call.

CD164L2 p.His161Asp

c.481C>G · VCV4222601

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4215	ambiguous
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 3,733 bp · p 0.73 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	0.000254%	393,338

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.His161Asp
Coding: c.481C>G
MANE Select: NM_001330448
Type: single nucleotide variant
Location: chr1:27380088 (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.Arg43Pro 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-his161asp (accessed [today's date]).

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