Is MYO7A p.Arg1977Trp (c.5929C>T) pathogenic?

MYO7A p.Arg1977Trp (c.5929C>T) is classified Uncertain significance in MYO7A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-04-01). AlphaMissense: ambiguous (0.5009); Ultra-rare (popmax 0.0164%, mid); Associated with retinitis pigmentosa.

What condition is associated with MYO7A p.Arg1977Trp (c.5929C>T)?

MYO7A p.Arg1977Trp (c.5929C>T) is associated with retinitis pigmentosa (ClinVar).

How common is MYO7A p.Arg1977Trp (c.5929C>T) in the general population?

MYO7A p.Arg1977Trp (c.5929C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MYO7A p.Arg1977Trp (c.5929C>T)?

AlphaMissense predicts ambiguous (score 0.5009) — an in-silico prediction, not a clinical call.

MYO7A p.Arg1977Trp

c.5929C>T · rs781586223 · VCV636222

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5009 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.5009	ambiguous
REVEL	0.614	indeterminate
SaProt	LLR -10.62	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.89	GERP -2.1, phastCons 0.15
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	24.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00124% 20/1,613,156 alleles · ultra-rare exomes 18/1,460,990 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Finnishnot grpmax-eligible	0.0141%	7,097
Admixed American	0.00334%	29,975
East Asian	0.00223%	44,880
South Asian	0.0022%	45,447
Remaining individualsnot grpmax-eligible	0.0016%	62,436
European (non-Finnish)	0.000339%	294,907

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.Arg1977Trp
Coding: c.5929C>T
MANE Select: NM_000260
dbSNP: rs781586223
Type: single nucleotide variant
Location: chr11:77208502 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1977: the ferm 2 domain

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

MYO7A p.Arg1977Gln Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg1977= Uncertain significance ★ same residue
MYO7A p.Cys31Ter Pathogenic ★★ same condition
MYO7A p.Pro541Arg Uncertain significance ★★ ⚠ same condition
MYO7A p.Met262Arg Likely pathogenic ★ same condition
MYO7A p.Glu1095Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
MYO7A c.3503+12G>A Likely benign ★ same condition
MYO7A p.Gly556Val 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-arg1977trp (accessed [today's date]).

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