Is MYO7B p.Tyr2008= (c.6024T>C) pathogenic?

MYO7B p.Tyr2008= (c.6024T>C) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele; Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Tyr2008= (c.6024T>C)?

MYO7B p.Tyr2008= (c.6024T>C) is associated with MYO7B-related disorder (ClinVar).

MYO7B p.Tyr2008=

Q: How common is MYO7B p.Tyr2008= (c.6024T>C) in the general population?

MYO7B p.Tyr2008= (c.6024T>C) is common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6024T>C · rs2255161 · VCV3055711

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele

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 -0.48	GERP -2.7
Overall
CADD	3.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.9% South Asian · 32,646/90,988 alleles

Filtering AF 35.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.4%

Overall 20.2% 326,043/1,611,722 alleles · common exomes 295,924/1,459,648 · genomes 30,119/152,074 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	35.9%	3
Finnishnot grpmax-eligible	22.6%	4
Middle Eastern	21.5%	5
Remaining individualsnot grpmax-eligible	19.9%	5
European (non-Finnish)	19.7%	5
African / African-American	18.8%	5
Ashkenazi Jewishnot grpmax-eligible	15.6%	6
East Asian	14.3%	7
Admixed American	13%	8
Amishnot grpmax-eligible	4.71%	21

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.Tyr2008=
Coding: c.6024T>C
MANE Select: NM_001393586
dbSNP: rs2255161
Type: single nucleotide variant
Location: chr2:127636225 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 2008: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region; a turn

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-tyr2008 (accessed [today's date]).

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