Is MYO7B p.His1684= (c.5052C>T) pathogenic?

MYO7B p.His1684= (c.5052C>T) is classified Likely benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Ultra-rare (popmax 0.0484%, amr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.His1684= (c.5052C>T)?

MYO7B p.His1684= (c.5052C>T) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.His1684= (c.5052C>T) in the general population?

MYO7B p.His1684= (c.5052C>T) is ultra-rare (popmax 0.0484%, amr) (gnomAD).

MYO7B p.His1684=

c.5052C>T · rs201376272 · VCV3045320

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0484%, amr)

Conditions

MYO7B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0484% Admixed American · 29/59,958 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00347% 56/1,611,764 alleles · ultra-rare exomes 50/1,459,534 · genomes 6/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0484%	2,068
South Asian	0.0022%	45,522
European (non-Finnish)	0.00204%	49,125
African / African-American	0.00133%	74,922

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: MYO7B
Protein: p.His1684=
Coding: c.5052C>T
MANE Select: NM_001393586
dbSNP: rs201376272
Type: single nucleotide variant
Location: chr2:127631320 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1684: the myth4 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.His1684Gln Uncertain significance ★ ⚠ same residue
MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign 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/myo7b-p-his1684 (accessed [today's date]).

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