Is MYO7A p.Ser1786Thr (c.5356T>A) pathogenic?

MYO7A p.Ser1786Thr (c.5356T>A) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.2079); Rare (popmax 0.198%, mid); Associated with Inborn genetic diseases.

What condition is associated with MYO7A p.Ser1786Thr (c.5356T>A)?

MYO7A p.Ser1786Thr (c.5356T>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYO7A p.Ser1786Thr (c.5356T>A) in the general population?

MYO7A p.Ser1786Thr (c.5356T>A) is rare (popmax 0.198%, mid) (gnomAD).

What do computational predictors say about MYO7A p.Ser1786Thr (c.5356T>A)?

AlphaMissense predicts likely benign (score 0.2079) — an in-silico prediction, not a clinical call.

MYO7A p.Ser1786Thr

c.5356T>A · rs374576916 · VCV178491

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2079 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.198%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2079	likely benign
REVEL	0.373	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.49, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	22.0	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 0.198% Middle Eastern · 12/6,054 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0896%

Overall 0.00799% 128/1,601,522 alleles · rare exomes 111/1,449,286 · genomes 17/152,236 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.198%	505
African / African-American	0.0308%	3,245
Remaining individualsnot grpmax-eligible	0.0129%	7,762
Admixed American	0.012%	8,368
European (non-Finnish)	0.00647%	15,452
South Asian	0.00227%	44,140

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.Ser1786Thr
Coding: c.5356T>A
MANE Select: NM_000260
dbSNP: rs374576916
Type: single nucleotide variant
Location: chr11:77204105 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1786: the myth4 2 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.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
MYO7A p.Ala1894Val 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-ser1786thr (accessed [today's date]).

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