Is CD1B p.Arg327Trp (c.979C>T) pathogenic?

CD1B p.Arg327Trp (c.979C>T) is classified Likely benign in CD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.0657); Ultra-rare (popmax 0.0167%, mid).

How common is CD1B p.Arg327Trp (c.979C>T) in the general population?

CD1B p.Arg327Trp (c.979C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about CD1B p.Arg327Trp (c.979C>T)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

CD1B p.Arg327Trp

c.979C>T · rs200467928 · VCV3140384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -9.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -3.7
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	4.577	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 0.0167% Middle Eastern · 1/5,972 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00457%

Overall 0.00507% 81/1,596,582 alleles · ultra-rare exomes 73/1,444,852 · genomes 8/151,730 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,972
East Asian	0.00671%	14,913
European (non-Finnish)	0.00614%	16,295
Admixed American	0.00356%	28,117
South Asian	0.00229%	43,684
Remaining individualsnot grpmax-eligible	0.00162%	61,756

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: CD1B
Protein: p.Arg327Trp
Coding: c.979C>T
MANE Select: NM_001764
dbSNP: rs200467928
Type: single nucleotide variant
Location: chr1:158328922 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB

Full CD1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1B p.Gly104Ser Benign ★★ same type
CD1B p.Gly247Ser Benign ★★ ⚠ same type
CD1B p.Phe76= Benign ★★ same type
CD1C p.Arg283Thr Likely benign ★★ same type
CD1C p.Gln23= Benign ★★ same type
CD1C p.Phe300Ser Benign ★★ same type
CD1C p.Val282Leu Likely benign ★★ ⚠ same type
CD1C p.Val318= 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/cd1b-p-arg327trp (accessed [today's date]).

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