Is MYO7B p.Leu1398= (c.4194C>T) pathogenic?

MYO7B p.Leu1398= (c.4194C>T) is classified Likely benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-06). Ultra-rare (popmax 0.0511%, amr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Leu1398= (c.4194C>T)?

MYO7B p.Leu1398= (c.4194C>T) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Leu1398= (c.4194C>T) in the general population?

MYO7B p.Leu1398= (c.4194C>T) is ultra-rare (popmax 0.0511%, amr) (gnomAD).

MYO7B p.Leu1398=

c.4194C>T · rs536153919 · VCV3044021

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0511%, amr)

Conditions

MYO7B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	donor loss · deltas
Pangolin	Δ0.24	loss · gain 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -7.9	GERP -3.3
Overall
CADD	0.608	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0511% Admixed American · 30/58,700 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0319%

Overall 0.00523% 84/1,605,082 alleles · ultra-rare exomes 46/1,452,752 · genomes 38/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0511%	1,957
Middle Eastern	0.0334%	2,995
South Asian	0.0288%	3,467
African / African-American	0.0187%	5,340
Remaining individualsnot grpmax-eligible	0.00806%	12,402
European (non-Finnish)	0.000595%	168,053

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: MYO7B
Protein: p.Leu1398=
Coding: c.4194C>T
MANE Select: NM_001393586
dbSNP: rs536153919
Type: single nucleotide variant
Location: chr2:127625514 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1398: the 'mediates interaction with anks4b' region; the ferm 1 domain

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign same condition
MYO7B c.6123+9T>C Benign 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/myo7b-p-leu1398 (accessed [today's date]).

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