Is MYH9 p.Ile703Phe (c.2107A>T) pathogenic?

MYH9 p.Ile703Phe (c.2107A>T) is classified Uncertain significance in MYH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2006-06-30). AlphaMissense: likely pathogenic (0.9929); Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 17.

What condition is associated with MYH9 p.Ile703Phe (c.2107A>T)?

MYH9 p.Ile703Phe (c.2107A>T) is associated with autosomal dominant nonsyndromic hearing loss 17 (ClinVar).

How common is MYH9 p.Ile703Phe (c.2107A>T) in the general population?

MYH9 p.Ile703Phe (c.2107A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYH9 p.Ile703Phe (c.2107A>T)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

MYH9 p.Ile703Phe

c.2107A>T · VCV4857395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 17

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic · top 10% in MYH9
REVEL	0.933	strongly pathogenic-leaning
SaProt	LLR -14.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 10 kb · p 1.8e-23 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYH9
Protein: p.Ile703Phe
Coding: c.2107A>T
MANE Select: NM_002473
Type: single nucleotide variant
Location: chr22:36305982 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 76.42 · 8 PDB
Residue 703: the myosin motor domain; the 'mediates interaction with limch1' region

Full MYH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant nonsyndromic hearing loss 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYH9 p.Ile703= Likely benign ★ same residue
MYH9 p.Arg1165Cys Pathogenic ★★ same condition
MYH9 p.Arg1933Ter Pathogenic ★★ same condition
MYH9 p.Arg702Cys Pathogenic ★★ same condition
MYH9 p.Arg705His Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Arg718Trp Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Asp1424Asn Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Glu1841Lys 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/myh9-p-ile703phe (accessed [today's date]).

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