Is CD1C p.Phe300Ser (c.899T>C) pathogenic?

CD1C p.Phe300Ser (c.899T>C) is classified Benign in CD1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-27). AlphaMissense: likely benign (0.0872); Common (popmax 7.81%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CD1C p.Phe300Ser (c.899T>C)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

CD1C p.Phe300Ser

Q: How common is CD1C p.Phe300Ser (c.899T>C) in the general population?

CD1C p.Phe300Ser (c.899T>C) is common (popmax 7.81%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.899T>C · rs3138105 · VCV773640

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.81%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -20	GERP -3.3
Regional constraint	o/e 1.06	unconstrained · MANE · 3,408 bp · p 0.27 · regional, not allelic
Overall
CADD	0.631	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 7.81% East Asian · 3,502/44,856 alleles

Filtering AF 7.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.5%

Overall 0.267% 4,312/1,613,520 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.81%	13
Remaining individualsnot grpmax-eligible	0.844%	119
South Asian	0.228%	438
Admixed American	0.0333%	3,001
African / African-American	0.028%	3,573
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.0028%	35,743

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: CD1C
Protein: p.Phe300Ser
Coding: c.899T>C
MANE Select: NM_001764 · reported on NM_001765
dbSNP: rs3138105
Type: single nucleotide variant
Location: chr1:158293221 (GRCh38)

Full CD1C 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/cd1c-p-phe300ser (accessed [today's date]).

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