Is TTC7A p.Lys4= (c.12G>A) pathogenic?

TTC7A p.Lys4= (c.12G>A) is classified Likely benign in TTC7A (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-05). Very rare (popmax 0.00242%, eas); Associated with multiple intestinal atresia.

What condition is associated with TTC7A p.Lys4= (c.12G>A)?

TTC7A p.Lys4= (c.12G>A) is associated with multiple intestinal atresia (ClinVar).

How common is TTC7A p.Lys4= (c.12G>A) in the general population?

TTC7A p.Lys4= (c.12G>A) is very rare (popmax 0.00242%, eas) (gnomAD).

TTC7A p.Lys4=

c.12G>A · rs1274237789 · VCV528468

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00242%, eas)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 0.97, phastCons 1
Overall
CADD	15.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00242% East Asian · 1/41,330 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000267%

Overall 0.000708% 11/1,554,684 alleles · very rare exomes 10/1,402,474 · genomes 1/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00242%	41,330
Finnishnot grpmax-eligible	0.00171%	58,564
European (non-Finnish)	0.000783%	127,739

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.Lys4=
Coding: c.12G>A
MANE Select: NM_020458
dbSNP: rs1274237789
Type: single nucleotide variant
Location: chr2:46941553 (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

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-lys4 (accessed [today's date]).

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