Is MYO7A p.Thr1841Arg (c.5522C>G) pathogenic?

MYO7A p.Thr1841Arg (c.5522C>G) is classified Pathogenic/Likely pathogenic in MYO7A (ClinVar, No assertion criteria, 2 submitters; last evaluated 2018-09-10). AlphaMissense: likely pathogenic (0.9859); Very rare (popmax 0.00114%, sas); Associated with hearing loss, autosomal recessive.

What condition is associated with MYO7A p.Thr1841Arg (c.5522C>G)?

MYO7A p.Thr1841Arg (c.5522C>G) is associated with hearing loss, autosomal recessive (ClinVar).

How common is MYO7A p.Thr1841Arg (c.5522C>G) in the general population?

MYO7A p.Thr1841Arg (c.5522C>G) is very rare (popmax 0.00114%, sas) (gnomAD).

How is Rare non-syndromic genetic deafness inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Thr1841Arg (c.5522C>G)?

AlphaMissense predicts likely pathogenic (score 0.9859) — an in-silico prediction, not a clinical call.

MYO7A p.Thr1841Arg

c.5522C>G · rs746667217 · VCV560894

Pathogenic/Likely pathogenic No assertion criteria

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9859 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9859	likely pathogenic ✓ concordant with ClinVar
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -17.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.8	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 0.00114% South Asian · 1/87,778 alleles

Overall 6.26e-05% 1/1,596,444 alleles · very rare exomes 1/1,444,138 · genomes 0/152,306 · 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: MYO7A
Protein: p.Thr1841Arg
Coding: c.5522C>G
MANE Select: NM_000260
dbSNP: rs746667217
Type: single nucleotide variant
Location: chr11:77205503 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1841: the myth4 2 domain; an α-helix

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

Disease context

hearing loss, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rare non-syndromic genetic deafness (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

MYO7A p.Thr1841Ala Uncertain significance ★★ ⚠ same residue
MYO7A p.Thr1841Met Uncertain significance ★★ ⚠ same residue
MYO7A p.Thr1841= Likely benign ★ same residue
MYO7A p.Thr1841Ser Uncertain significance ⚠ same residue
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Leu326Gln Likely pathogenic ★★★ same condition
MYO7A p.Ser617Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg241His Pathogenic/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-thr1841arg (accessed [today's date]).

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