Is TMEM67 p.Lys897fs (c.2689_2690insTA) pathogenic?

TMEM67 p.Lys897fs (c.26892690insTA) is classified Likely pathogenic in TMEM67 (ClinVar, No assertion criteria, 1 submitter). No gnomAD frequency available for this variant; Associated with Meckel syndrome, type 3.

What condition is associated with TMEM67 p.Lys897fs (c.2689_2690insTA)?

TMEM67 p.Lys897fs (c.2689_2690insTA) is associated with Meckel syndrome, type 3 (ClinVar).

How common is TMEM67 p.Lys897fs (c.2689_2690insTA) in the general population?

TMEM67 p.Lys897fs (c.2689_2690insTA) is no gnomAD frequency available for this variant (gnomAD).

TMEM67 p.Lys897fs

c.2689_2690insTA · rs386834198 · VCV56779

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Meckel syndrome, type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMEM67
Protein: p.Lys897fs
Coding: c.2689_2690insTA
MANE Select: NM_153704
dbSNP: rs386834198
Type: Insertion
Location: chr8:93809811 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.20 · 1 PDB
Residue 897: a β-strand; a UniProt-annotated variant site (in jbts6); a UniProt-annotated variant site (in jbts6, mks3 and rhyns); a UniProt-annotated variant site (in mks3)

Full TMEM67 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meckel syndrome, type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TMEM67 c.1413-2A>G Pathogenic/Likely pathogenic ★★ same condition
TMEM67 c.224-2del Pathogenic/Likely pathogenic ★★ same condition
TMEM67 c.2764+2T>G Likely pathogenic ★★ same condition
TMEM67 c.312+1G>A Pathogenic/Likely pathogenic ★★ same condition
TMEM67 c.312+5G>A Pathogenic ★★ same condition
TMEM67 c.869+1G>C Likely pathogenic ★★ same condition
TMEM67 c.978+1G>A Likely pathogenic ★★ same condition
TMEM67 p.Ala447fs 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/tmem67-p-lys897fs (accessed [today's date]).

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