Is CD101 p.Trp526Arg (c.1576T>C) pathogenic?

CD101 p.Trp526Arg (c.1576T>C) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.4166); Ultra-rare (popmax 0.014%, nfe).

How common is CD101 p.Trp526Arg (c.1576T>C) in the general population?

CD101 p.Trp526Arg (c.1576T>C) is ultra-rare (popmax 0.014%, nfe) (gnomAD).

What do computational predictors say about CD101 p.Trp526Arg (c.1576T>C)?

AlphaMissense predicts ambiguous (score 0.4166) — an in-silico prediction, not a clinical call.

CD101 p.Trp526Arg

c.1576T>C · rs375022404 · VCV3140256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4166	ambiguous
REVEL	0.253	benign-leaning
SaProt	LLR -1.00	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 4.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	22.9	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 0.014% European (non-Finnish) · 165/1,179,388 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0107% 172/1,613,276 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.014%	7,148
Remaining individualsnot grpmax-eligible	0.00961%	10,407
Admixed American	0.00167%	59,998

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: CD101
Protein: p.Trp526Arg
Coding: c.1576T>C
MANE Select: NM_001256106
dbSNP: rs375022404
Type: single nucleotide variant
Location: chr1:117017437 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76

Full CD101 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD101 p.Arg622His Benign ★★ same type
CD101 p.Arg933Gln Benign ★★ ⚠ same type
CD101 p.Asn225Ser Benign ★★ same type
CD101 p.Leu362Pro Benign ★★ same type
CD101 p.Ser525Arg Benign ★★ ⚠ same type
CD101 p.Ser985= Benign ★★ same type
CD101 p.Tyr651Asp Benign ★★ same type
CD101 p.Ala195Thr 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/cd101-p-trp526arg (accessed [today's date]).

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