Is MYO7A p.Val1236Leu (c.3706G>C) pathogenic?

MYO7A p.Val1236Leu (c.3706G>C) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-31). AlphaMissense: likely benign (0.1218); Very rare (popmax 0.00929%, eas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Val1236Leu (c.3706G>C)?

MYO7A p.Val1236Leu (c.3706G>C) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Val1236Leu (c.3706G>C) in the general population?

MYO7A p.Val1236Leu (c.3706G>C) is very rare (popmax 0.00929%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Val1236Leu (c.3706G>C)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

MYO7A p.Val1236Leu

c.3706G>C · rs1591413336 · VCV1312572

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00929%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -7.17	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 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.2	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 0.00929% East Asian · 4/43,064 alleles

Filtering AF 0.00316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00186%

Overall 0.000317% 5/1,579,386 alleles · very rare exomes 0/1,427,012 · genomes 5/152,374 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00929%	10,766
Remaining individualsnot grpmax-eligible	0.00163%	61,216

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: MYO7A
Protein: p.Val1236Leu
Coding: c.3706G>C
MANE Select: NM_000260
dbSNP: rs1591413336
Type: single nucleotide variant
Location: chr11:77190095 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1236: the myth4 1 domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Val1236= Likely benign ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely 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/myo7a-p-val1236leu (accessed [today's date]).

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