Is MYO7B p.Ser701Leu (c.2102C>T) pathogenic?

MYO7B p.Ser701Leu (c.2102C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1014); Rare (popmax 0.108%, eas).

How common is MYO7B p.Ser701Leu (c.2102C>T) in the general population?

MYO7B p.Ser701Leu (c.2102C>T) is rare (popmax 0.108%, eas) (gnomAD).

What do computational predictors say about MYO7B p.Ser701Leu (c.2102C>T)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

MYO7B p.Ser701Leu

c.2102C>T · VCV3916366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -0.87, phastCons 0.008
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	19.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.108% East Asian · 48/44,520 alleles

Filtering AF 0.0835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0749%

Overall 0.00311% 50/1,606,110 alleles · rare exomes 44/1,453,734 · genomes 6/152,376 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.108%	927
Admixed American	0.00169%	59,222
Remaining individualsnot grpmax-eligible	0.00161%	62,228

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.Ser701Leu
Coding: c.2102C>T
MANE Select: NM_001393586
Type: single nucleotide variant
Location: chr2:127592903 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 701: 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.Ile1309Val Benign ★★ same type
MYO7B p.Val1556Ile Benign ★★ same type
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
MYO7B p.Ala1126Thr Uncertain significance ★ ⚠ same type

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-ser701leu (accessed [today's date]).

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