Is MYO7A p.Arg900Leu (c.2699G>T) pathogenic?

MYO7A p.Arg900Leu (c.2699G>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: ambiguous (0.4629); Very rare (popmax 0.000866%, nfe); Associated with autosomal dominant nonsyndromic hearing loss 11.

What condition is associated with MYO7A p.Arg900Leu (c.2699G>T)?

MYO7A p.Arg900Leu (c.2699G>T) is associated with autosomal dominant nonsyndromic hearing loss 11 (ClinVar).

How common is MYO7A p.Arg900Leu (c.2699G>T) in the general population?

MYO7A p.Arg900Leu (c.2699G>T) is very rare (popmax 0.000866%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Arg900Leu (c.2699G>T)?

AlphaMissense predicts ambiguous (score 0.4629) — an in-silico prediction, not a clinical call.

MYO7A p.Arg900Leu

c.2699G>T · VCV3376697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000866%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal dominant nonsyndromic hearing loss 11

Computational evidence

Protein change
AlphaMissense	0.4629	ambiguous
REVEL	0.771	pathogenic-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	25.1	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 0.000866% European (non-Finnish) · 10/1,154,416 alleles

Filtering AF 0.000438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000319%

Overall 0.000833% 13/1,561,432 alleles · very rare exomes 12/1,409,182 · genomes 1/152,250 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0033%	30,308
Finnishnot grpmax-eligible	0.00172%	58,274
European (non-Finnish)grpmax	0.000866%	115,442

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg900Leu
Coding: c.2699G>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77181384 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 900: the 'sah' region

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

Disease context

autosomal dominant nonsyndromic hearing loss 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Arg900Cys Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg900His 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
MYO7A p.Glu968Asp 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-arg900leu (accessed [today's date]).

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