Is TULP1 p.Lys193= (c.579G>A) pathogenic?

TULP1 p.Lys193= (c.579G>A) is classified Likely benign in TULP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-13). Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with TULP1 p.Lys193= (c.579G>A)?

TULP1 p.Lys193= (c.579G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TULP1 p.Lys193= (c.579G>A) in the general population?

TULP1 p.Lys193= (c.579G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

TULP1 p.Lys193=

c.579G>A · rs377091740 · VCV2083819

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -0.71
Overall
CADD	8.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,900 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000682% 11/1,614,004 alleles · very rare exomes 4/1,461,878 · genomes 7/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,700
Remaining individualsnot grpmax-eligible	0.0032%	31,243
South Asian	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,034

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: TULP1
Protein: p.Lys193=
Coding: c.579G>A
MANE Select: NM_003322
dbSNP: rs377091740
Type: single nucleotide variant
Location: chr6:35509849 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 193: the 'disordered' region

Full TULP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP1 p.Ala221Val Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala496Val Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala524Thr Uncertain significance ★★ ⚠ same condition
TULP1 p.Ala531Thr Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg159Ser Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg308Gln Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg344Gln Uncertain significance ★★ ⚠ same condition
TULP1 p.Arg416His Uncertain significance ★★ 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/tulp1-p-lys193 (accessed [today's date]).

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