Is MYO7A p.His1853Asn (c.5557C>A) pathogenic?

MYO7A p.His1853Asn (c.5557C>A) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.6261); Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.His1853Asn (c.5557C>A)?

MYO7A p.His1853Asn (c.5557C>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.His1853Asn (c.5557C>A) in the general population?

MYO7A p.His1853Asn (c.5557C>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about MYO7A p.His1853Asn (c.5557C>A)?

AlphaMissense predicts likely pathogenic (score 0.6261) — an in-silico prediction, not a clinical call.

MYO7A p.His1853Asn

c.5557C>A · VCV4625610

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6261	likely pathogenic
REVEL	0.71	pathogenic-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.41	acceptor loss, 9 bp away · masked 0 · 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	29.3	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 0.00668% African / African-American · 5/74,796 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000311% 5/1,609,754 alleles · very rare exomes 2/1,457,536 · genomes 3/152,218 · joint denominator

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.His1853Asn
Coding: c.5557C>A
MANE Select: NM_000260
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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.His1853= Benign/Likely benign ★★ same residue
MYO7A p.His1853Asp Uncertain significance ★ ⚠ same residue
MYO7A p.His1853Gln Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ 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-his1853asn (accessed [today's date]).

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