Is MYOT p.Gln135Pro (c.404A>C) pathogenic?

MYOT p.Gln135Pro (c.404A>C) is classified Uncertain significance in MYOT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.0906); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYOT p.Gln135Pro (c.404A>C)?

MYOT p.Gln135Pro (c.404A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MYOT p.Gln135Pro (c.404A>C) in the general population?

MYOT p.Gln135Pro (c.404A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about MYOT p.Gln135Pro (c.404A>C)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

MYOT p.Gln135Pro

c.404A>C · rs748726301 · VCV2605216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -5.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.27, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 17 kb · p 0.00034 · regional, not allelic
Overall
CADD	17.48	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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) · 4/1,179,992 alleles

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

Overall 0.000274% 4/1,461,804 alleles · very rare

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: MYOT
Protein: p.Gln135Pro
Coding: c.404A>C
MANE Select: NM_006790
dbSNP: rs748726301
Type: single nucleotide variant
Location: chr5:137875876 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.17 · 2 PDB
Residue 135: the 'disordered' region; the 'necessary for interaction with actn1' region

Full MYOT 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

MYOT p.Ala131Glu Uncertain significance ★★ ⚠ same condition
MYOT p.Arg178Cys Uncertain significance ★★ same condition
MYOT p.Arg188Ile Uncertain significance ★★ ⚠ same condition
MYOT p.Arg188Lys Uncertain significance ★★ same condition
MYOT p.Asn445Lys Uncertain significance ★★ ⚠ same condition
MYOT p.Gln254His Uncertain significance ★★ ⚠ same condition
MYOT p.Gln371His Uncertain significance ★★ ⚠ same condition
MYOT p.Gly175Glu 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/myot-p-gln135pro (accessed [today's date]).

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