Is TULP1 p.Val412Met (c.1234G>A) pathogenic?

TULP1 p.Val412Met (c.1234G>A) is classified Uncertain significance in TULP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: ambiguous (0.5364); Very rare (popmax 0.00681%, eas); Associated with inherited retinal dystrophy.

What condition is associated with TULP1 p.Val412Met (c.1234G>A)?

TULP1 p.Val412Met (c.1234G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is TULP1 p.Val412Met (c.1234G>A) in the general population?

TULP1 p.Val412Met (c.1234G>A) is very rare (popmax 0.00681%, eas) (gnomAD).

What do computational predictors say about TULP1 p.Val412Met (c.1234G>A)?

AlphaMissense predicts ambiguous (score 0.5364) — an in-silico prediction, not a clinical call.

TULP1 p.Val412Met

c.1234G>A · rs761670562 · VCV3027735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00681%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.5364	ambiguous
REVEL	0.919	moderately pathogenic-leaning
SaProt	LLR -11.24	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.1, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 7,948 bp · p 0.64 · regional, not allelic
Overall
CADD	26.5	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 0.00681% East Asian · 3/44,082 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00119% 19/1,599,302 alleles · very rare exomes 16/1,447,090 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00681%	14,694
Admixed American	0.00345%	28,984
Remaining individualsnot grpmax-eligible	0.00162%	61,884
South Asian	0.00113%	88,406
European (non-Finnish)	0.00102%	97,774

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.Val412Met
Coding: c.1234G>A
MANE Select: NM_003322
dbSNP: rs761670562
Type: single nucleotide variant
Location: chr6:35503648 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.10 · 2 PDB
Residue 412: an α-helix

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TULP1 c.1496-6C>A Pathogenic/Likely pathogenic ★★ same condition
TULP1 c.718+2T>C Pathogenic ★★ same condition
TULP1 p.Arg361Ter Pathogenic ★★ same condition
TULP1 p.Arg400Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg419Trp Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Arg440Ter Pathogenic ★★ same condition
TULP1 p.Asn349Lys Pathogenic/Likely pathogenic ★★ same condition
TULP1 p.Gln401Ter 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/tulp1-p-val412met (accessed [today's date]).

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