Is MYO7A p.Ser1940Leu (c.5819C>T) pathogenic?

MYO7A p.Ser1940Leu (c.5819C>T) is classified Likely pathogenic in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.1716); Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 2.

What condition is associated with MYO7A p.Ser1940Leu (c.5819C>T)?

MYO7A p.Ser1940Leu (c.5819C>T) is associated with autosomal recessive nonsyndromic hearing loss 2 (ClinVar).

How common is MYO7A p.Ser1940Leu (c.5819C>T) in the general population?

MYO7A p.Ser1940Leu (c.5819C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MYO7A p.Ser1940Leu (c.5819C>T)?

AlphaMissense predicts likely benign (score 0.1716) — an in-silico prediction, not a clinical call.

MYO7A p.Ser1940Leu

c.5819C>T · VCV3601493

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 2

Computational evidence

Protein change
AlphaMissense	0.1716	likely benign ⚠ discordant with ClinVar
REVEL	0.244	benign-leaning
SaProt	LLR -10.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -0.74, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.5	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 8.48e-05% European (non-Finnish) · 1/1,178,968 alleles

Overall 6.2e-05% 1/1,611,714 alleles · very rare exomes 1/1,459,404 · genomes 0/152,310 · 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.Ser1940Leu
Coding: c.5819C>T
MANE Select: NM_000260
Type: single nucleotide variant
Location: chr11:77207365 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1940: the ferm 2 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.Ser1940= Conflicting classifications of pathogenicity ★ 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
MYO7A p.Gly2187Asp 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-ser1940leu (accessed [today's date]).

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