Is TTC7A p.Phe64fs (c.192del) pathogenic?

TTC7A p.Phe64fs (c.192del) is classified Pathogenic/Likely pathogenic in TTC7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-22). Very rare (popmax 0.00203%, nfe); Associated with gastrointestinal defects and immunodeficiency syndrome 1.

How common is TTC7A p.Phe64fs (c.192del) in the general population?

TTC7A p.Phe64fs (c.192del) is very rare (popmax 0.00203%, nfe) (gnomAD).

TTC7A p.Phe64fs

Q: What condition is associated with TTC7A p.Phe64fs (c.192del)?

TTC7A p.Phe64fs (c.192del) is associated with gastrointestinal defects and immunodeficiency syndrome 1, multiple intestinal atresia (ClinVar).

Q: How is Combined immunodeficiency-multiple intestinal atresia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.192del · rs1476031758 · VCV1071145

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Conditions

gastrointestinal defects and immunodeficiency syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,968 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.0018% 29/1,613,958 alleles · very rare exomes 29/1,461,662 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)grpmax	0.00203%	49,165
African / African-American	0.00133%	75,010

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TTC7A
Protein: p.Phe64fs
Coding: c.192del
MANE Select: NM_020458
dbSNP: rs1476031758
Type: Deletion
Location: chr2:46950368 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.59

Full TTC7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gastrointestinal defects and immunodeficiency syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple intestinal atresia

For Combined immunodeficiency-multiple intestinal atresia (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

TTC7A p.Phe64Tyr Uncertain significance ★ ⚠ same residue
TTC7A p.Asn104_Tyr105insTer Pathogenic ★★ same condition
TTC7A p.Leu304fs Pathogenic/Likely pathogenic ★★ same condition
TTC7A p.Leu544fs Pathogenic/Likely pathogenic ★★ same condition
TTC7A c.1287+1del Likely pathogenic ★ same condition
TTC7A p.Ala755fs Pathogenic ★ same condition
TTC7A p.Glu595fs Pathogenic ★ same condition
TTC7A p.Leu819_Gly827del Pathogenic ★ 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/ttc7a-p-phe64fs (accessed [today's date]).

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