Is MYO7A p.His1853Asp (c.5557C>G) pathogenic?

MYO7A p.His1853Asp (c.5557C>G) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.938); Very rare (popmax 0.00224%, eas).

How common is MYO7A p.His1853Asp (c.5557C>G) in the general population?

MYO7A p.His1853Asp (c.5557C>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about MYO7A p.His1853Asp (c.5557C>G)?

AlphaMissense predicts likely pathogenic (score 0.938) — an in-silico prediction, not a clinical call.

MYO7A p.His1853Asp

c.5557C>G · rs370192806 · VCV1504944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.938 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.938	likely pathogenic
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.46	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	32.0	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 0.00224% East Asian · 1/44,734 alleles

Overall 0.000186% 3/1,609,754 alleles · very rare exomes 2/1,457,536 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,734
Admixed American	0.00168%	59,572
African / African-American	0.00134%	74,796

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.His1853Asp
Coding: c.5557C>G
MANE Select: NM_000260
dbSNP: rs370192806
Type: single nucleotide variant
Location: chr11:77205538 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1853: 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.His1853= Benign/Likely benign ★★ same residue
MYO7A p.His1853Asn Uncertain significance ★ ⚠ same residue
MYO7A p.His1853Gln Uncertain significance ★ ⚠ 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-his1853asp (accessed [today's date]).

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