Is MYO7A p.Arg848Gln (c.2543G>A) pathogenic?

MYO7A p.Arg848Gln (c.2543G>A) is classified Uncertain significance in MYO7A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-27). AlphaMissense: ambiguous (0.5259); Very rare (popmax 0.000437%, nfe); Associated with Monogenic hearing loss.

What condition is associated with MYO7A p.Arg848Gln (c.2543G>A)?

MYO7A p.Arg848Gln (c.2543G>A) is associated with Monogenic hearing loss (ClinVar).

How common is MYO7A p.Arg848Gln (c.2543G>A) in the general population?

MYO7A p.Arg848Gln (c.2543G>A) is very rare (popmax 0.000437%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg848Gln (c.2543G>A)?

AlphaMissense predicts ambiguous (score 0.5259) — an in-silico prediction, not a clinical call.

MYO7A p.Arg848Gln

c.2543G>A · rs1555082917 · VCV1434969

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000437%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Monogenic hearing loss

Computational evidence

Protein change
AlphaMissense	0.5259	ambiguous
REVEL	0.693	pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense 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	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 0.000437% European (non-Finnish) · 5/1,143,850 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000326% 5/1,535,536 alleles · very rare exomes 4/1,383,292 · genomes 1/152,244 · 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.Arg848Gln
Coding: c.2543G>A
MANE Select: NM_000260
dbSNP: rs1555082917
Type: single nucleotide variant
Location: chr11:77179910 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 848: the iq 5 domain

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

Disease context

Monogenic hearing loss

Similar variants

MYO7A p.Arg848Gly Uncertain significance ★ ⚠ same residue
MYO7A p.Arg848Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYO7A c.133-2A>G Pathogenic ★★ same condition
MYO7A c.1344-2A>G Pathogenic ★★ same condition
MYO7A c.1690+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.18+1G>A Pathogenic/Likely pathogenic ★★ same condition
MYO7A c.19-1G>A Likely pathogenic ★★ same condition
MYO7A c.2187+1G>A Pathogenic/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-arg848gln (accessed [today's date]).

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