Is CD101 p.Arg814Cys (c.2440C>T) pathogenic?

CD101 p.Arg814Cys (c.2440C>T) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.1029); Very rare (popmax 0.00683%, afr).

How common is CD101 p.Arg814Cys (c.2440C>T) in the general population?

CD101 p.Arg814Cys (c.2440C>T) is very rare (popmax 0.00683%, afr) (gnomAD).

What do computational predictors say about CD101 p.Arg814Cys (c.2440C>T)?

AlphaMissense predicts likely benign (score 0.1029) — an in-silico prediction, not a clinical call.

CD101 p.Arg814Cys

c.2440C>T · rs371042116 · VCV3140264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00683%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1029	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -11.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.32	GERP -0.44
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	20.3	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 0.00683% African / African-American · 5/73,180 alleles

Filtering AF 0.00387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00425% 66/1,554,126 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00683%	14,636
European (non-Finnish)	0.00495%	20,190
Remaining individualsnot grpmax-eligible	0.00334%	29,975
Admixed American	0.00189%	52,784
South Asian	0.00119%	84,338

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: CD101
Protein: p.Arg814Cys
Coding: c.2440C>T
MANE Select: NM_001256106
dbSNP: rs371042116
Type: single nucleotide variant
Location: chr1:117025520 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 814: the ig-like c2-type 7 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-arg814cys (accessed [today's date]).

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