Is CD1B p.Gly247Ser (c.739G>A) pathogenic?

CD1B p.Gly247Ser (c.739G>A) is classified Benign in CD1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-11). AlphaMissense: likely benign (0.1316); Low-frequency (popmax 3.27%, afr).

How common is CD1B p.Gly247Ser (c.739G>A) in the general population?

CD1B p.Gly247Ser (c.739G>A) is low-frequency (popmax 3.27%, afr) (gnomAD).

What do computational predictors say about CD1B p.Gly247Ser (c.739G>A)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

CD1B p.Gly247Ser

c.739G>A · rs61745679 · VCV775614

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -0.057
Regional constraint	o/e 1.23	unconstrained · MANE · 3,184 bp · p 5.6e-06 · regional, not allelic
Overall
CADD	16.51	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 3.27% African / African-American · 2,454/75,020 alleles

Filtering AF 3.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.194% 3,129/1,614,142 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Admixed American	0.392%	255
Remaining individualsnot grpmax-eligible	0.304%	329
Middle Eastern	0.297%	337
Finnishnot grpmax-eligible	0.0187%	5,336
European (non-Finnish)	0.018%	5,566
South Asian	0.00878%	11,385

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.Gly247Ser
Coding: c.739G>A
MANE Select: NM_001764
dbSNP: rs61745679
Type: single nucleotide variant
Location: chr1:158329517 (GRCh38)
Gene constraint: LOEUF 1.334 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.00 · 28 PDB
Residue 247: a disulfide bond; the ig-like domain

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

Similar variants

CD1B p.Gly104Ser 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
CD1B p.Ala10Thr 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/cd1b-p-gly247ser (accessed [today's date]).

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