Is TTC7A p.Arg808Met (c.2423G>T) pathogenic?

TTC7A p.Arg808Met (c.2423G>T) is classified Uncertain significance in TTC7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: likely benign (0.139); Very rare (popmax 0.00333%, amr); Associated with multiple intestinal atresia.

What condition is associated with TTC7A p.Arg808Met (c.2423G>T)?

TTC7A p.Arg808Met (c.2423G>T) is associated with multiple intestinal atresia (ClinVar).

How common is TTC7A p.Arg808Met (c.2423G>T) in the general population?

TTC7A p.Arg808Met (c.2423G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TTC7A p.Arg808Met (c.2423G>T)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

TTC7A p.Arg808Met

c.2423G>T · rs377401476 · VCV2176387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple intestinal atresia

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP -1.5, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 132 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	24.4	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 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,613,736 alleles · very rare exomes 15/1,461,512 · genomes 5/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
European (non-Finnish)	0.00153%	65,557

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.Arg808Met
Coding: c.2423G>T
MANE Select: NM_020458
dbSNP: rs377401476
Type: single nucleotide variant
Location: chr2:47073769 (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.Arg808= 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
TTC7A p.Cys623Ter 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-arg808met (accessed [today's date]).

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