Is MYO7A p.Pro1418= (c.4254C>T) pathogenic?

MYO7A p.Pro1418= (c.4254C>T) is classified Likely benign in MYO7A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0331%, mid); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Pro1418= (c.4254C>T)?

MYO7A p.Pro1418= (c.4254C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Pro1418= (c.4254C>T) in the general population?

MYO7A p.Pro1418= (c.4254C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

MYO7A p.Pro1418=

c.4254C>T · rs548434591 · VCV227685

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -12	GERP -2.6
Overall
CADD	0.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,050 alleles

Filtering AF 0.0064% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00615% 99/1,610,654 alleles · ultra-rare exomes 85/1,458,348 · genomes 14/152,306 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,025
European (non-Finnish)	0.00772%	12,952
Remaining individualsnot grpmax-eligible	0.00321%	31,175
Finnishnot grpmax-eligible	0.00313%	31,911
African / African-American	0.00267%	37,483

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.Pro1418=
Coding: c.4254C>T
MANE Select: NM_000260
dbSNP: rs548434591
Type: single nucleotide variant
Location: chr11:77194455 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1418: the ferm 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Pro1418Arg Uncertain significance ★ ⚠ same residue
MYO7A p.Ser1471Pro Pathogenic/Likely pathogenic ★★ same condition
MYO7A p.Ala1005Thr Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1203Ser Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1335Asp Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1551Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala1563Val Uncertain significance ★★ ⚠ same condition
MYO7A p.Ala162Thr Uncertain significance ★★ ⚠ 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-pro1418 (accessed [today's date]).

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