Is CD101 p.Arg88Trp (c.262C>T) pathogenic?

CD101 p.Arg88Trp (c.262C>T) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.3936); Ultra-rare (popmax 0.078%, sas).

How common is CD101 p.Arg88Trp (c.262C>T) in the general population?

CD101 p.Arg88Trp (c.262C>T) is ultra-rare (popmax 0.078%, sas) (gnomAD).

What do computational predictors say about CD101 p.Arg88Trp (c.262C>T)?

AlphaMissense predicts ambiguous (score 0.3936) — an in-silico prediction, not a clinical call.

CD101 p.Arg88Trp

c.262C>T · rs367625011 · VCV3140265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, sas)

Computational evidence

Protein change
AlphaMissense	0.3936	ambiguous
REVEL	0.525	indeterminate
SaProt	LLR -15.16	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.96, phastCons 0.94
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	23.7	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 0.078% South Asian · 71/91,082 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.007% 113/1,614,038 alleles · ultra-rare exomes 106/1,461,860 · genomes 7/152,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.078%	1,283
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.00288%	34,707
East Asian	0.00223%	44,894
African / African-American	0.00133%	74,920

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.Arg88Trp
Coding: c.262C>T
MANE Select: NM_001256106
dbSNP: rs367625011
Type: single nucleotide variant
Location: chr1:117010068 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 88: the ig-like c2-type 1 domain

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-arg88trp (accessed [today's date]).

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