Is TTC7A p.Pro59Arg (c.176C>G) pathogenic?

TTC7A p.Pro59Arg (c.176C>G) is classified Conflicting classifications of pathogenicity in TTC7A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0865); Rare (popmax 0.643%, nfe); Associated with multiple intestinal atresia.

What condition is associated with TTC7A p.Pro59Arg (c.176C>G)?

TTC7A p.Pro59Arg (c.176C>G) is associated with multiple intestinal atresia, gastrointestinal defects and immunodeficiency syndrome 1 (ClinVar).

How common is TTC7A p.Pro59Arg (c.176C>G) in the general population?

TTC7A p.Pro59Arg (c.176C>G) is rare (popmax 0.643%, nfe) (gnomAD).

What do computational predictors say about TTC7A p.Pro59Arg (c.176C>G)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

TTC7A p.Pro59Arg

c.176C>G · rs201805434 · VCV528474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.643%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple intestinal atresia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.097	GERP -1.4, phastCons 0.001
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	2.065	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 0.643% European (non-Finnish) · 7,376/1,147,114 alleles

Filtering AF 0.631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.626%

Overall 0.535% 8,299/1,550,222 alleles · rare exomes 7,817/1,397,868 · genomes 482/152,354 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.643%	156
Ashkenazi Jewishnot grpmax-eligible	0.576%	173
Remaining individualsnot grpmax-eligible	0.518%	193
Amishnot grpmax-eligible	0.439%	228
South Asian	0.284%	352
Middle Eastern	0.207%	483
Admixed American	0.204%	491
African / African-American	0.0765%	1,307
Finnishnot grpmax-eligible	0.0548%	1,826

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.Pro59Arg
Coding: c.176C>G
MANE Select: NM_020458
dbSNP: rs201805434
Type: single nucleotide variant
Location: chr2:46941717 (GRCh38)

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

Disease context

multiple intestinal atresia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal defects and immunodeficiency syndrome 1

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-pro59arg (accessed [today's date]).

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