Is TTC7A p.Pro855Arg (c.2564C>G) pathogenic?

TTC7A p.Pro855Arg (c.2564C>G) is classified Uncertain significance in TTC7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-24). AlphaMissense: likely benign (0.2087); Very rare (popmax 0.00229%, nfe); Associated with multiple intestinal atresia.

What condition is associated with TTC7A p.Pro855Arg (c.2564C>G)?

TTC7A p.Pro855Arg (c.2564C>G) is associated with multiple intestinal atresia (ClinVar).

How common is TTC7A p.Pro855Arg (c.2564C>G) in the general population?

TTC7A p.Pro855Arg (c.2564C>G) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about TTC7A p.Pro855Arg (c.2564C>G)?

AlphaMissense predicts likely benign (score 0.2087) — an in-silico prediction, not a clinical call.

TTC7A p.Pro855Arg

c.2564C>G · rs750794132 · VCV1035571

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

multiple intestinal atresia

Computational evidence

Protein change
AlphaMissense	0.2087	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,394 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00168% 27/1,611,810 alleles · very rare exomes 25/1,459,566 · genomes 2/152,244 · joint denominator

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.Pro855Arg
Coding: c.2564C>G
MANE Select: NM_020458
dbSNP: rs750794132
Type: single nucleotide variant
Location: chr2:47073910 (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

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

Similar variants

TTC7A p.Pro855Leu Uncertain significance ★ ⚠ same residue
TTC7A p.Pro855= Likely benign ★ same residue
TTC7A c.1288-1G>T Pathogenic/Likely pathogenic ★★ same condition
TTC7A c.1641+1G>A 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

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-pro855arg (accessed [today's date]).

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