Is CD101 p.Arg548Cys (c.1642C>T) pathogenic?

CD101 p.Arg548Cys (c.1642C>T) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: ambiguous (0.5127); Ultra-rare (popmax 0.025%, nfe).

How common is CD101 p.Arg548Cys (c.1642C>T) in the general population?

CD101 p.Arg548Cys (c.1642C>T) is ultra-rare (popmax 0.025%, nfe) (gnomAD).

What do computational predictors say about CD101 p.Arg548Cys (c.1642C>T)?

AlphaMissense predicts ambiguous (score 0.5127) — an in-silico prediction, not a clinical call.

CD101 p.Arg548Cys

c.1642C>T · rs370564335 · VCV3140259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5127 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5127	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	29.6	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 0.025% European (non-Finnish) · 293/1,174,030 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.0201% 322/1,604,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.025%	4,007
Finnishnot grpmax-eligible	0.0188%	5,324
Remaining individualsnot grpmax-eligible	0.0177%	5,641
African / African-American	0.00669%	14,937
East Asian	0.00224%	44,696

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.Arg548Cys
Coding: c.1642C>T
MANE Select: NM_001256106
dbSNP: rs370564335
Type: single nucleotide variant
Location: chr1:117018185 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 548: the ig-like c2-type 5 domain

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

Similar variants

CD101 p.Arg548His Uncertain significance ★ ⚠ same residue
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

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-arg548cys (accessed [today's date]).

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