Is TTI1 p.Lys544= (c.1632A>G) pathogenic?

TTI1 p.Lys544= (c.1632A>G) is classified Likely benign in TTI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.000339%, nfe).

How common is TTI1 p.Lys544= (c.1632A>G) in the general population?

TTI1 p.Lys544= (c.1632A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

TTI1 p.Lys544=

c.1632A>G · VCV4821416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.98	GERP -4.4
Overall
CADD	1.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,038 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,614,188 alleles · very rare exomes 6/1,461,872 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)grpmax	0.000339%	295,010

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TTI1
Protein: p.Lys544=
Coding: c.1632A>G
MANE Select: NM_001303457
Type: single nucleotide variant
Location: chr20:38012185 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38 · 3 PDB
Residue 544: a UniProt-annotated variant site (in nedmim; likely pathogenic)

Full TTI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TTI1 p.Ala806Thr Uncertain significance ★★ ⚠ same type
TTI1 p.Arg519Gln Uncertain significance ★★ ⚠ same type
TTI1 p.Arg724Gly Uncertain significance ★★ ⚠ same type
TTI1 p.Arg869Cys Uncertain significance ★★ same type
TTI1 p.Cys86Tyr Uncertain significance ★★ ⚠ same type
TTI1 p.His229Tyr Uncertain significance ★★ ⚠ same type
TTI1 p.His513Tyr Uncertain significance ★★ ⚠ same type
TTI1 p.Ile634Thr Uncertain significance ★★ ⚠ same type

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/tti1-p-lys544 (accessed [today's date]).

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