Is TULP1 p.Glu331Lys (c.991G>A) pathogenic?

TULP1 p.Glu331Lys (c.991G>A) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.183); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TULP1 p.Glu331Lys (c.991G>A)?

TULP1 p.Glu331Lys (c.991G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TULP1 p.Glu331Lys (c.991G>A) in the general population?

TULP1 p.Glu331Lys (c.991G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about TULP1 p.Glu331Lys (c.991G>A)?

AlphaMissense predicts likely benign (score 0.183) — an in-silico prediction, not a clinical call.

TULP1 p.Glu331Lys

c.991G>A · VCV3812445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.183 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.183	likely benign
REVEL	0.4	indeterminate
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP -0.36, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,036 alleles

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

Overall 0.000248% 4/1,614,128 alleles · very rare exomes 4/1,461,782 · genomes 0/152,346 · joint denominator

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.Glu331Lys
Coding: c.991G>A
MANE Select: NM_003322
Type: single nucleotide variant
Location: chr6:35506011 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 331: a β-strand

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-glu331lys (accessed [today's date]).

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