Is CD101 p.Arg992Trp (c.2974C>T) pathogenic?

CD101 p.Arg992Trp (c.2974C>T) is classified Benign in CD101 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0834); Common (popmax 7.17%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD101 p.Arg992Trp (c.2974C>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

CD101 p.Arg992Trp

Q: How common is CD101 p.Arg992Trp (c.2974C>T) in the general population?

CD101 p.Arg992Trp (c.2974C>T) is common (popmax 7.17%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2974C>T · rs34248572 · VCV780258

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.17%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.21	GERP -0.5
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	15.91	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 7.17% African / African-American · 5,374/74,952 alleles

Filtering AF 7.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.94%

Overall 0.383% 6,178/1,614,030 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.17%	14
Admixed American	0.538%	186
Remaining individualsnot grpmax-eligible	0.467%	214
Middle Eastern	0.231%	433
South Asian	0.0318%	3,141
European (non-Finnish)	0.012%	8,310
East Asian	0.00446%	22,437
Finnishnot grpmax-eligible	0.00312%	32,002

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.Arg992Trp
Coding: c.2974C>T
dbSNP: rs34248572
Type: single nucleotide variant
Location: chr1:117034009 (GRCh38)

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

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-arg992trp (accessed [today's date]).

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