Is MYO7A p.His545Arg (c.1634A>G) pathogenic?

MYO7A p.His545Arg (c.1634A>G) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-05). AlphaMissense: likely benign (0.1641); Ultra-rare (popmax 0.0231%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.His545Arg (c.1634A>G)?

MYO7A p.His545Arg (c.1634A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.His545Arg (c.1634A>G) in the general population?

MYO7A p.His545Arg (c.1634A>G) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about MYO7A p.His545Arg (c.1634A>G)?

AlphaMissense predicts likely benign (score 0.1641) — an in-silico prediction, not a clinical call.

MYO7A p.His545Arg

c.1634A>G · rs781981689 · VCV2137409

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1641	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -4.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	20.7	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 0.0231% South Asian · 21/91,048 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00192% 31/1,613,632 alleles · ultra-rare exomes 29/1,461,686 · genomes 2/151,946 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,336
Remaining individualsnot grpmax-eligible	0.0144%	6,939
European (non-Finnish)	8.48e-05%	1,179,832

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.His545Arg
Coding: c.1634A>G
MANE Select: NM_000260
dbSNP: rs781981689
Type: single nucleotide variant
Location: chr11:77162932 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 545: the myosin motor domain

Full MYO7A 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

MYO7A p.His545= Likely benign ★★ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr 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/myo7a-p-his545arg (accessed [today's date]).

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