Is CCDC47 p.Arg271Ter (c.811C>T) pathogenic?

CCDC47 p.Arg271Ter (c.811C>T) is classified Likely pathogenic in CCDC47 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-09-24). Very rare (popmax 0.000424%, nfe); Associated with Global developmental delay with dysmorphic features, liver dysfunction, pruritus, and woolly hair.

How common is CCDC47 p.Arg271Ter (c.811C>T) in the general population?

CCDC47 p.Arg271Ter (c.811C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

CCDC47 p.Arg271Ter

Q: What condition is associated with CCDC47 p.Arg271Ter (c.811C>T)?

CCDC47 p.Arg271Ter (c.811C>T) is associated with Global developmental delay with dysmorphic features, liver dysfunction, pruritus, and woolly hair, trichohepatoneurodevelopmental syndrome (ClinVar).

c.811C>T · rs749027804 · VCV562186

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

Global developmental delay with dysmorphic features, liver dysfunction, pruritus, and woolly hair

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 4.4, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,514 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,314 alleles · very rare

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: CCDC47
Protein: p.Arg271Ter
Coding: c.811C>T
MANE Select: NM_020198
dbSNP: rs749027804
Type: single nucleotide variant
Location: chr17:63756495 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07 · 1 PDB
Residue 271: a UniProt-annotated variant site (in thns; loss-of-function variant affecting er calcium ion homeostasis in patient cells; no protein detected by western blot in patient cells)

Full CCDC47 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Global developmental delay with dysmorphic features, liver dysfunction, pruritus, and woolly hair

Also linked: trichohepatoneurodevelopmental syndrome

Similar variants

CCDC47 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same condition
CCDC47 c.1093+112G>A Benign ★★ same condition
CCDC47 c.735+15C>T Benign ★★ same condition
CCDC47 c.669+5G>T Uncertain significance ★ same condition
CCDC47 p.Ile58Leu Uncertain significance ★ same condition
CCDC47 p.Leu299Ser Uncertain significance ★ ⚠ same condition
CCDC47 c.948+9G>A Likely benign same condition
CCDC47 c.-10T>A Benign same condition

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/ccdc47-p-arg271ter (accessed [today's date]).

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