Is CD1A p.Phe140Ser (c.419T>C) pathogenic?

CD1A p.Phe140Ser (c.419T>C) is classified Uncertain significance in CD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.6182); Very rare (popmax 0.00891%, eas).

How common is CD1A p.Phe140Ser (c.419T>C) in the general population?

CD1A p.Phe140Ser (c.419T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CD1A p.Phe140Ser (c.419T>C)?

AlphaMissense predicts likely pathogenic (score 0.6182) — an in-silico prediction, not a clinical call.

CD1A p.Phe140Ser

c.419T>C · rs763791970 · VCV2490371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6182	likely pathogenic · top 6% in CD1A
REVEL	0.164	moderately benign-leaning
SaProt	LLR -10.56	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.62, phastCons 0.13
Regional constraint	o/e 1.13	unconstrained · MANE · 3,017 bp · p 0.0086 · regional, not allelic
Overall
CADD	17.95	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 0.00891% East Asian · 4/44,876 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000342% 5/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,219
European (non-Finnish)	8.47e-05%	1,180,004

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: CD1A
Protein: p.Phe140Ser
Coding: c.419T>C
MANE Select: NM_001763
dbSNP: rs763791970
Type: single nucleotide variant
Location: chr1:158256097 (GRCh38)
Gene constraint: LOEUF 1.644 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.11 · 16 PDB
Residue 140: a disulfide bond; a β-strand

Full CD1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD1A c.605-3C>T Benign ★★ same type
CD1A p.Arg90Cys Benign ★★ ⚠ same type
CD1A p.Gly240Asp Likely benign ★★ ⚠ same type
CD1A p.Ala102Thr Uncertain significance ★ ⚠ same type
CD1A p.Ala196Glu Uncertain significance ★ ⚠ same type
CD1A p.Ala196Ser Uncertain significance ★ ⚠ same type
CD1A p.Ala264Pro Uncertain significance ★ ⚠ same type
CD1A p.Ala306Val 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/cd1a-p-phe140ser (accessed [today's date]).

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