Is MYO7B p.Ile487Thr (c.1460T>C) pathogenic?

MYO7B p.Ile487Thr (c.1460T>C) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: ambiguous (0.5477); Rare (popmax 0.124%, sas).

How common is MYO7B p.Ile487Thr (c.1460T>C) in the general population?

MYO7B p.Ile487Thr (c.1460T>C) is rare (popmax 0.124%, sas) (gnomAD).

What do computational predictors say about MYO7B p.Ile487Thr (c.1460T>C)?

AlphaMissense predicts ambiguous (score 0.5477) — an in-silico prediction, not a clinical call.

MYO7B p.Ile487Thr

c.1460T>C · rs61742021 · VCV3166118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5477 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5477	ambiguous
REVEL	0.956	strongly pathogenic-leaning
SaProt	LLR -11.63	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	26.3	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 0.124% South Asian · 113/91,082 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0985%

Overall 0.0159% 257/1,613,950 alleles · rare exomes 231/1,461,706 · genomes 26/152,244 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.23%	435
South Asiangrpmax	0.124%	806
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Admixed American	0.0333%	3,001
Middle Eastern	0.033%	3,031
African / African-American	0.00267%	37,507
European (non-Finnish)	0.00237%	42,139

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile487Thr
Coding: c.1460T>C
MANE Select: NM_001393586
dbSNP: rs61742021
Type: single nucleotide variant
Location: chr2:127584238 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 487: the myosin motor domain

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

Similar variants

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MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ same type
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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-ile487thr (accessed [today's date]).

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