Is MYO7A p.Asp1797Asn (c.5389G>A) pathogenic?

MYO7A p.Asp1797Asn (c.5389G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-03). AlphaMissense: likely pathogenic (0.8369); Very rare (popmax 0.00403%, afr).

How common is MYO7A p.Asp1797Asn (c.5389G>A) in the general population?

MYO7A p.Asp1797Asn (c.5389G>A) is very rare (popmax 0.00403%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Asp1797Asn (c.5389G>A)?

AlphaMissense predicts likely pathogenic (score 0.8369) — an in-silico prediction, not a clinical call.

MYO7A p.Asp1797Asn

c.5389G>A · rs376674270 · VCV2052818

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8369 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00403%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8369	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00403% African / African-American · 3/74,482 alleles

Filtering AF 0.00233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00203%

Overall 0.00269% 43/1,598,758 alleles · very rare exomes 40/1,446,524 · genomes 3/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00403%	24,827
European (non-Finnish)	0.00315%	31,704
Admixed American	0.00172%	58,170
Remaining individualsnot grpmax-eligible	0.00161%	61,984
South Asian	0.00114%	87,892

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.Asp1797Asn
Coding: c.5389G>A
MANE Select: NM_000260
dbSNP: rs376674270
Type: single nucleotide variant
Location: chr11:77204138 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1797: the myth4 2 domain; an α-helix

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

Similar variants

MYO7A p.Asp1797Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Asp1797= Likely benign ★ same residue
MYO7A p.Asp1797fs Pathogenic ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type

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-asp1797asn (accessed [today's date]).

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