Is MYO7A p.Arg616Gln (c.1847G>A) pathogenic?

MYO7A p.Arg616Gln (c.1847G>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-20). AlphaMissense: ambiguous (0.4488); Very rare (popmax 0.00726%, eas); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Arg616Gln (c.1847G>A)?

MYO7A p.Arg616Gln (c.1847G>A) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Arg616Gln (c.1847G>A) in the general population?

MYO7A p.Arg616Gln (c.1847G>A) is very rare (popmax 0.00726%, eas) (gnomAD).

What do computational predictors say about MYO7A p.Arg616Gln (c.1847G>A)?

AlphaMissense predicts ambiguous (score 0.4488) — an in-silico prediction, not a clinical call.

MYO7A p.Arg616Gln

c.1847G>A · rs782410686 · VCV1028643

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00726%, eas)

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.4488	ambiguous
REVEL	0.291	indeterminate
SaProt	LLR -3.52	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.43, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	27.0	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 0.00726% East Asian · 3/41,316 alleles

Filtering AF 0.00193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00186% 29/1,558,486 alleles · very rare exomes 26/1,406,274 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00726%	13,772
African / African-American	0.00546%	18,328
Remaining individualsnot grpmax-eligible	0.00331%	30,208
Admixed American	0.00192%	51,972
Finnishnot grpmax-eligible	0.00167%	60,060
European (non-Finnish)	0.00156%	63,972

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.Arg616Gln
Coding: c.1847G>A
MANE Select: NM_000260
dbSNP: rs782410686
Type: single nucleotide variant
Location: chr11:77172797 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 616: the myosin motor domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg616Trp Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg616= Likely benign ★ same residue
MYO7A p.Arg616Leu Uncertain significance ⚠ same residue
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

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-arg616gln (accessed [today's date]).

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