Is MYO7B p.Ala1216= (c.3648T>G) pathogenic?

MYO7B p.Ala1216= (c.3648T>G) is classified Likely benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-06). Rare (popmax 0.325%, nfe); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Ala1216= (c.3648T>G)?

MYO7B p.Ala1216= (c.3648T>G) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Ala1216= (c.3648T>G) in the general population?

MYO7B p.Ala1216= (c.3648T>G) is rare (popmax 0.325%, nfe) (gnomAD).

MYO7B p.Ala1216=

c.3648T>G · rs188404852 · VCV3039099

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.325%, nfe)

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 -4.9	GERP -3.5
Overall
CADD	1.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.325% European (non-Finnish) · 3,829/1,179,744 alleles

Filtering AF 0.316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.312%

Overall 0.26% 4,198/1,613,460 alleles · rare exomes 3,899/1,461,234 · genomes 299/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.325%	308
Remaining individualsnot grpmax-eligible	0.213%	470
Admixed American	0.173%	577
Finnishnot grpmax-eligible	0.143%	700
African / African-American	0.0347%	2,884
South Asian	0.0165%	6,073

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.Ala1216=
Coding: c.3648T>G
MANE Select: NM_001393586
dbSNP: rs188404852
Type: single nucleotide variant
Location: chr2:127623204 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1216: the 'mediates interaction with anks4b' region; the ferm 1 domain

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

Disease context

MYO7B-related disorder

Similar variants

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
MYO7B c.6123+9T>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-ala1216 (accessed [today's date]).

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