Is MYO7A p.Asp2049Asn (c.6145G>A) pathogenic?

MYO7A p.Asp2049Asn (c.6145G>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-17). AlphaMissense: likely benign (0.2468); Very rare (popmax 0.00348%, sas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Asp2049Asn (c.6145G>A)?

MYO7A p.Asp2049Asn (c.6145G>A) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Asp2049Asn (c.6145G>A) in the general population?

MYO7A p.Asp2049Asn (c.6145G>A) is very rare (popmax 0.00348%, sas) (gnomAD).

What do computational predictors say about MYO7A p.Asp2049Asn (c.6145G>A)?

AlphaMissense predicts likely benign (score 0.2468) — an in-silico prediction, not a clinical call.

MYO7A p.Asp2049Asn

c.6145G>A · rs1336095094 · VCV989490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
AlphaMissense	0.2468	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	26.1	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 0.00348% South Asian · 3/86,260 alleles

Filtering AF 0.000924% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000456%

Overall 0.000442% 7/1,584,650 alleles · very rare exomes 6/1,432,454 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00348%	28,753
European (non-Finnish)	0.000343%	291,417

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.Asp2049Asn
Coding: c.6145G>A
MANE Select: NM_000260
dbSNP: rs1336095094
Type: single nucleotide variant
Location: chr11:77211245 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 2049: the ferm 2 domain

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

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Gly2187Asp 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-asp2049asn (accessed [today's date]).

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