Is TTC7A p.Ala798Val (c.2393C>T) pathogenic?

TTC7A p.Ala798Val (c.2393C>T) is classified Likely pathogenic in TTC7A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). AlphaMissense: likely pathogenic (0.7829); Absent from gnomAD v4.1; Associated with gastrointestinal defects and immunodeficiency syndrome 1.

What condition is associated with TTC7A p.Ala798Val (c.2393C>T)?

TTC7A p.Ala798Val (c.2393C>T) is associated with gastrointestinal defects and immunodeficiency syndrome 1 (ClinVar).

How common is TTC7A p.Ala798Val (c.2393C>T) in the general population?

TTC7A p.Ala798Val (c.2393C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTC7A p.Ala798Val (c.2393C>T)?

AlphaMissense predicts likely pathogenic (score 0.7829) — an in-silico prediction, not a clinical call.

TTC7A p.Ala798Val

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

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

c.2393C>T · VCV3255331

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7829 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal defects and immunodeficiency syndrome 1

Computational evidence

Protein change
AlphaMissense	0.7829	likely pathogenic ✓ concordant with ClinVar
REVEL	0.74	pathogenic-leaning
SaProt	LLR -15.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	28.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTC7A
Protein: p.Ala798Val
Coding: c.2393C>T
MANE Select: NM_020458
Type: single nucleotide variant
Location: chr2:47073739 (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

For Combined immunodeficiency-multiple intestinal atresia (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

TTC7A p.Ala798= Likely benign ★ same residue
TTC7A c.1288-1G>T Pathogenic/Likely pathogenic ★★ same condition
TTC7A c.2018-1G>C Pathogenic/Likely pathogenic ★★ same condition
TTC7A p.Arg138Ter Pathogenic/Likely pathogenic ★★ same condition
TTC7A p.Arg358Ter Pathogenic/Likely pathogenic ★★ same condition
TTC7A p.Arg405Ter Pathogenic/Likely pathogenic ★★ same condition
TTC7A p.Cys623Ter Pathogenic ★★ same condition
TTC7A p.Gln526Ter 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-ala798val (accessed [today's date]).

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